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Anticancer activities considering cell cytotoxicity, apoptosis and molecular docking have been explored in Zn(ii) co-crystals of phenanthroline involving infinite chair-like assemblies and unconventional layered infinite anion-water clusters.

In vitro anticancer activities have been explored in fumarato and phthalato bridged dinuclear Cu(ii) and Mn(ii) compounds involving infinite fumarate–water assemblies and unusual structure-guiding H-bonded synthons.

Anticancer activities considering cell viability, apoptosis and molecular docking have been explored in dinuclear Zn(ii) and polymeric Mn(ii) compounds involving energetically significant unconventional N(nitrile)⋯π(fum) contacts.

Alstonia scholaris, Cardiospermum halicacabum, Hydrocotyle sibthorpioides, and Hypericum japonicum are important folk medicinal plants used by tribal communities of Bodoland region of Assam to treat helminth infections. Because of their ethnomedicinal values, the present study was designed to investigate the antioxidant, antiproliferative, and anthelmintic activities of the plants. The antioxidant activity was measured by total antioxidant capacity, total phenolics (TPC), total flavonoid (TFC), FRAP, DPPH, ABTS, and TBARS assay. Antiproliferative and apoptosis-inducing activities of plants were conducted in Dalton’s lymphoma (DL) cells. Cells were treated for 24 h with different doses (25–200 mg/mL) of plant extracts. Anthelmintic study was conducted by treating the Paramphistomum sp. at different doses of plant extracts. Phytochemical and antioxidant studies showed rich TPC, TFC, and free radical scavenging activity in H. japonicum and H. sibthorpioides. Both the antiproliferative and anthelmintic bioassays showed a dose-dependent efficacy in all plants. H. japonicum showed the strongest anthelmintic activity (LC(50) 0.21 mg/mL) followed by H. sibthorpioides (5.36 mg/mL), C. halicacabum (13.40 mg/mL), and A. scholaris (18.40 mg/mL). Evidently, H. sibthorpioides showed the strongest antiproliferative and apoptosis-inducing activities among all the plants. The study observed a positive correlation between the antioxidant properties and antiproliferative and anthelmintic activities of the plants. We, therefore, conclude that the phytocompounds present in the crude extracts along with antioxidant molecules may have combined effects contributing to the antiproliferative and anthelmintic activities of the plants.

Two new coordination complexes of Cu(II) viz.; [Cu(bpy)2(NO3)]NO3·5H2O (1) and [Cu(phen)(Hdmpz)Cl2]·H2O (2) (bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline, Hdmpz = 3,5-dimethyl pyrazole) have been synthesized and characterized by single crystal X-ray diffraction, electronic spectroscopy, EPR, FT-IR spectroscopy and TGA. The nitrate anion and the water molecules in the lattice of 1 are involved in the formation of unconventional infinite supramolecular crown-like nitrate–water clusters. The unconventional enclathration of guest cationic complex moieties of 1 within the supramolecular nitrate–water crown hosts provides stability to the crystal structure. Crystal structure analysis of 2 reveals the presence of cooperative ternary π-stacked assemblies with enclathration of single guest water molecules in hexameric Cu(II) supramolecular host cavities. Theoretical calculations have been performed to analyse the non-covalent interactions in the compounds; focusing on the unusual H-bonding network/anion–π cooperative assemblies in 1 and two different π-stacked cooperative assemblies in 2. DFT studies reveal that the distribution and orientation of the H-bonds in the cooperative H-bonding network in 1 is the most favoured. The high interaction energies of (π–π)1 and (π–π)2 in π-stacked ternary assemblies of 2 can be attributed to the participation of the entire aromatic surfaces with antiparallel orientations and the cooperative C–H⋯Cl interactions respectively. The in vitro antiproliferative activities of the compounds considering cell cytotoxicity, apoptosis and DNA fragmentation assays reveal significant concentration dependent cytotoxicity in DL cancer cells with nominal effects in normal PBMC cells. The molecular docking and pharmacophore studies established the structure activity relationship of the compounds.

Two new coordination polymers of Zn(II), viz. {[Zn(Hdmpz)2(μ-male)]·(MeOH)(H2O)}n (1) and [Zn(3-AMpy)2(μ-fum)(H2O)2]n (2) (where Hdmpz = 3,5-dimethylpyrazole, male = maleate, fum = fumarate, and 3-AMpy = 3-aminopyridine), have been synthesized and characterized using elemental analysis, TGA, spectroscopic and single crystal X-ray diffraction techniques. The 1D polymeric chains of the polymers self-assemble into 2D supramolecular architectures via several non-covalent interactions. Differences in the structural topologies have been observed with the change of solvent from the methanol–water mixture in compound 1 to de-ionized water in compound 2. Unconventional enclathration of the solvent molecules, viz. MeOH, and the water in the crystal structure of 1 results in an interesting layered assembly. The influences of the metal coordination on the strength of the π-stacking interactions have been explored theoretically for compound 2, which confirms that the coordination of 3-AMpy to the Zn(II) centre strongly polarizes the π-cloud and increases the local dipole of 3-AMpy, thereby enhancing the strength of π-stacking interactions. The in vitro anticancer activities of the compounds have been explored in Dalton's lymphoma cancer cell lines considering cell cytotoxicity and apoptosis, and the results were compared with those observed for cisplatin (reference drug) under the same experimental conditions. The in silico molecular docking studies and the pharmacophore features further corroborate the cytotoxicity and apoptosis inducing ability of the compounds.

Two new coordination compounds involving hexanuclear Cu(ii), viz., [Cu6(phen)6(μ4-adpt)4(H2O)2](NO3)4·10H2O (1) and polymeric Co(ii), viz., {[(μ2-adpt)4Co(μ2-H2O)2Co(H2O)4]·4H2O}n (2) (phen = 1,10-phenanthroline; adpt = adipate) have been synthesized and characterized using elemental analysis, TGA, spectroscopic (IR, electronic and ESR), PXRD and single crystal X-ray diffraction techniques. Discrete nitrate-water clusters involving the [(H2O)3NO3]- core in 1 and linear (H2O)4 core in 2 provide stability to the layered network of the structures of the compounds. Interestingly, the water clusters in polymer 2 are encapsulated as guests in the voids of the host square grid that extends in 2D architecture. Theoretical studies have revealed the presence of interesting energetically significant cooperativity effects of π-stacking contacts that are responsible for the hexanuclear structure of compound 1. Both complexes significantly inhibit cell viability by inducing apoptotic cell death in the DL cancer cell line with negligible cytotoxicity in normal cells (PBMC). An assessment of ROS (reactive oxygen species) level study revealed a rapid increase of ROS in DL cells indicating cytotoxicity of the compounds against the DL cells. A decrease in MMP (mitochondrial membrane potential) is associated with an opening of the mitochondrial permeability transition pores which corroborates the apoptotic features of 1 and 2. The mode of action of the cytotoxic activities of the compounds has been explored with respect to their in silico docking ability and further inhibition of antiapoptotic proteins as evidenced by western blot analysis. SAR analyses based on pharmacophore modelling reveal that the molecular features of the structures of the compounds play important roles in biological activities.

Two new coordination complexes of Cu(II) and Mn(II), viz., [Cu(bpy)(H2O)4]SO4·2H2O (1) and [Mn(4-CNpy)2(H2O)3SO4]·H2O (2) (bpy = 2,2′-bipyridine, 4-CNpy = 4-cyanopyridine), have been synthesized and characterized by using single crystal X-ray diffraction, elemental analysis, FT-IR spectroscopy, electronic spectroscopic techniques and TGA. The crystal structure of 1 uncovers the formation of sulfate–water assemblies involving lattice and coordinated water molecules, while complex 2 reveals the presence of unconventional weak T-shaped CN⋯CN contacts in the layered architecture. We have analysed the unconventional interesting interactions using DFT calculations, molecular electrostatic potential (MEP), the NCI plot and QTAIM computational tools. The interaction energies of the two H-bonded dimers in 1 are very large because of the coulombic attraction between the dicationic H-bonded donor and the dianionic acceptor. It is interesting to observe that despite the energy of the H-bonds being very small compared to the total dimerization energy, the final geometry of the assembly in 1 is due to the charge assisted directional H-bonds instead of the non-directional ion-pair interactions. The DFT study reveals that the T-shaped CN⋯CN interaction in 2 is very weak, in good agreement with the small MEP energy at the nitrile carbon atom. Anticancer studies of the compounds have been carried out using Dalton's lymphoma cell line using MTT and apoptosis assay. The results of compound 1 and 2 mediated cell cytotoxicity on the DL cancer cell line showed a significant concentration-dependent reduction in cell viability, while negligible cytotoxicity was observed in normal (PBMC) cells. The docking simulation results also confirm the interaction of the complexes with the active sites of amino acids of the target proteins. Furthermore, pharmacophore models (2D and 3D) for the compounds were mapped to the H-bond donor, positive ionisable area and hydrophobic features that are important for establishing biological activities. No hematotoxicity was recorded for the compounds after treatment in normal mice.

A new oxalato bridged polymeric Mn(III) coordination compound, {[Mn2(η2-C2O4)(H2O)2Cl4] 2(4-CNpy)}n (1) (C2O4 = oxalate, 4-CNpy = 4-cyanopyridine), has been synthesized and characterized using elemental analysis, and spectroscopic (IR, electronic, XPS) and single crystal X-ray diffraction techniques. Electronic and XPS analyses of the compound justify the presence of a Mn(III) center that is charge compensated by the two chlorido ligands and the oxygen atom of the bridged oxalate. 4-CNpy molecules in the lattice form unconventional H-bonded supramolecular dimers in the solid state assisted by antiparallel CN⋯CN dipole⋯dipole interactions, which has been confirmed using QTAIM and NCI plot analysis and supported by MEP surface analysis. Remarkably, this dimer concurrently establishes a weak anion–π interaction with the coordinated chlorido ligand. Unexpectedly, QTAIM analysis reveals the existence of an interesting O⋯π-hole(nitrile) contact involving the coordinated water molecule and the nitrile moiety that also contributes to the stabilization of the dimer in the crystal structure. To the best of our knowledge, the existence of such π-hole interaction involving nitrile derivatives has not been reported before. Compound 1 has been further screened for anticancer activity in the malignant Dalton's lymphoma (DL) cell line and the results were confirmed by molecular docking and pharmacophore features. Our findings indicated that the cytotoxicity of compound 1 is initially increased in a dose dependent manner (0.01–1 μM) and then decreased (5–10 μM), which is also affected by the reactive oxygen species (ROS) in the cells. Interestingly, very low cytotoxicity (5–14%) was observed in the case of healthy cells (PBMC) for similar experimental conditions.

Two new coordination compounds, viz., [Co(phen)(bz)(H2O)3]·bz (1) and [Zn(phen)2(H2O)Cl]·Cl·bzH·2H2O (2) (phen = 1,10-phenanthroline, bz = benzoate, bzH = benzoic acid) were synthesized from purely aqueous media, and characterized using elemental analysis, spectroscopic (IR, UV-Vis-NIR) and single crystal X-ray diffraction techniques. In the crystal structures of 1 and 2, supramolecular networks have been built involving the association of O–H⋯O, C–H⋯O, and π–π stacking interactions. The enclathration of the guest bzH molecule in the host monomers of Zn(II) brings rigidity to the structure of compound 2. Theoretical investigations have been carried out to rationalize interesting supramolecular assemblies that include cooperative anion–π/π–π/π–anion in 1 and DNA-relevant HB-array⋯π/π–π/π–HB-array interactions in 2, which have been characterized using NCI plots and Bader's theory of “atoms-in-molecules”. The complexes significantly inhibit cell viability by inducing apoptotic cell death in a Dalton's lymphoma (DL) cell line with negligible cytotoxicity in normal cells. A molecular docking study and pharmacophore features reveal that compounds 1 and 2 interact and are accommodated well in the active site of anti-apoptotic proteins. Antimicrobial studies against a few pathogenic organisms suggest that the compounds are active against Gram-positive and Gram-negative bacteria and have relatively better antibacterial activity in comparison to phen.

Graphical abstract, Highlights • Murraya koenigii induced higher cytotoxicity in Dalton’s lymphoma through apoptotic cell death as compared to other plants under study. • The plant extract mediated apoptotic cell death is mediated by ROS generation and caspases activation. • The study support the ethnomedicinal uses of these plants extracts and suggests further validation in other human cancer cell lines. • Conservation organization would eventually need to document this indigenous traditional knowledge (TK)., Annonareticulate (Mart.), Lablab purpureus (L.) Sweet, Murrayakoenigii (L.) Spreng, Moringaoleifera (Lam.), Hibiscussabdariffa (L.) and Euphorbiahirta (L.) are most commonly used medicinal plants by the traditional healers of Karbi Anglong district of Assam, India against different human ailments including cancer suspected cases. The proposed study includes field survey related to ethnomedicinal aspects of medicinal plants, phytochemical analysis, and evaluation of their cytostatic potential with the possible mode of action against Dalton's lymphoma (DL) cell line. The phytochemical analysis of all the plant's extract was studied using standard protocol. The cytotoxicity of the methanol extracts was determined by MTT reduction assay. The effect of the same extract was also tested for development of apoptosis features in DL cells using a fluorescence microscope and flowcytometry. The underlying mechanism closely associated with apoptotic cell death was also studied by measuring reactive oxygen species (ROS), mitochondrial membrane potential, and expression level of apoptosis inducing proteins. Murraya koenigii induced more apoptotic features in DL cells, followed by Annona reticulate. The decrease in mitochondrial membrane potential, release of cytochrome- c, increase in ROS level and higher expression of caspases (3 and 9) after plant extracts treatment may cause involvement of mitochondria in the process of apoptosis. From this study, it can be concluded that the plant species mainly Murraya koenigi and Annona reticulate significantly induced cytotoxicity in DL cells through apoptosis by utilizing mitochondrial pathway.

Two new Ni(II) coordination complexes of pyrazole and acetato ligands, involving nitrate and chloride counter anions, viz. [Ni(Hdmpz)2(CH3COO)(H2O)3]NO3·2H2O (1) and [Ni(Hdmpz)2(CH3COO)(H2O)3]Cl (2) (where Hdmpz = 3,5-dimethylpyrazole), have been synthesized in purely aqueous medium at room temperature. The complexes have been characterized by elemental analysis, FT-IR, electronic spectroscopy, PXRD, TGA and single crystal X-ray diffraction. The H-bonds established between the isostructural cationic [Ni(Hdmpz)2(CH3COO)(H2O)3]+ moieties of both complexes can be classified as anti-electrostatic H-bonds (AEHBs) and these have been studied using DFT calculations. Remarkably, in one case these AEHBs exhibit favorable interaction energies, thus indicating that the attractive nature of the H-bonds is able to compensate the pure electrostatic repulsion. The analyses of the cell viability results for the DL cell line show a significant concentration dependent decrease by compounds 1 and 2 with a negligible cytotoxic effect observed against normal cells (PBMC) in comparison to the cancer cells (DL). The cytotoxic activity of these compounds in DL cells occurs via apoptosis. Molecular docking and SAR analysis reveal that the compounds possess high binding affinities against most common cancer target proteins.

A new fumarato bridged Zn(II) coordination polymer viz. catena[μ-fumaratobis(3,5-dimethylpyrazole)zinc(II)trihydrate],{[Zn2(μ-fum)2(Hdmpz)4]·3H2O}n (1) (where, fum = fumarate, Hdmpz = 3,5-dimethylpyrazole) has been synthesized in purely aqueous medium at room temperature. The compound is structurally characterized by single crystal X-ray diffraction, FT-IR, electronic spectroscopy, PXRD and TGA. The zig-zag polymeric chain of 1 self assembles into a 2D supramolecular network via C H⋯π, C H⋯C, N H⋯O and C H⋯O interactions. Particularly relevant in 1, since in addition to the aforementioned non-covalent interactions, the electron rich π-system of fumarate is involved in energetically significant unconventional π–π contacts with the electron poor π-cloud of Hdmpz, which have been analyzed by DFT calculations and characterized using the non-covalent interaction (NCI) plot index. The strong H-bond agrees well with the MEP analysis since it is established between the H-bond donor involving NH group of Hdmpz and the H-bond acceptor involving O-atom of carboxylate moiety. The compound has been investigated for anticancer activities considering cell cytotoxicity, apoptosis and molecular docking as parameters in Dalton’s lymphoma (DL) malignant cancer cell line and results were compared with cisplatin (reference drug) under the same experimental conditions. Interestingly, negligible cytotoxic effect was observed against normal cells (PBMC) in comparison to the cancer cells (DL). The treatment of the compound caused appearance of apoptotic cells as evident by fluorescence based nuclear morphology study. The in silico study reveals that the compound interacts with the antiapoptotic proteins such as bcl-2, bcl-XL and Mcl-1 which may lead to apoptotic cell death.

Two new coordination solids [Cu2(μ2-Bz)4(CH3OH)2][Cu2(η2-Bz)2(phen)2(H2O)2]·(NO3)2 (1) and [Cu(phen)(H2O)(Bz)(η2-Bz)] (2) (phen = 1,10-phenanthroline; Bz = benzoate) have been synthesized and characterized using elemental analysis, TGA, spectroscopic (IR, UV-vis-NIR and ESR) and single crystal X-ray diffraction techniques. Change of the solvent from methanol to DMF results in changes in the architectures that are triggered by a change from square pyramidal to octahedral coordination at the divalent metal centers for complexes 1 and 2 respectively. The structural topology of the complexes is established by the interplay of strong O–H⋯O and weak C–H⋯O, C–H⋯C, π–π stacking interactions. Unconventional parallel intramolecular and anti-parallel intermolecular contacts involving the chelate rings (CR) also stabilize the structures. The energetic analyses of the structures evidence that the parallel arrangement is energetically favoured which is likely due to the presence of the Cu⋯Cu cuprophilic interaction in 1 that is not established in 2. Compound 1 exhibits the highest antibacterial activity against Rhizobium leguminosarum among the tested cultures. In vitro cytotoxicity and apoptosis studies were carried out for compounds 1 and 2 on malignant Dalton's lymphoma cell line (DL). Both compounds showed a significant effect on the decrease in cell viability as compared to a control, while compound 2 induced remarkable cytotoxicity towards DL cells. Treatment also showed the appearance of membrane blebbing, chromatin condensation and fragmented nuclei which are typical characteristic features of apoptotic cell death. Furthermore, a docking study revealed that both compounds docked in the active sites of all the cancer target proteins under study. Moreover, SAR analysis revealed that oxygen and nitrogen atoms of compound 1 and the oxygen atoms of compound 2 are crucial for biological activities.

People living in far-flung areas of the world, especially ethnic tribal people practice traditional medicine as the first choice of disease treatment. The present study investigates the antioxidant, cytotoxicity, and anthelmintic activity of four medicinal plants traditionally used by tribal communities of Bodoland Region of Assam. Total phenolic and flavonoid content was estimated following spectrophotometry method. Antioxidant activity was measured by total antioxidant assay, FRAP, DPPH, ABTS, and TBARS assay. Antiproliferative and apoptosis-inducing activity of plants were carried out in DL cells. Cells were treated for 24 h with different doses of plant extracts. Furthermore, anthelmintic study was carried out by treating the helminth parasite at different doses of plant extracts. Phytochemical and antioxidant study showed rich TPC, TFC, and free radical scavenging activity in H. japonicum and H. sibthorpioides. Both the antiproliferative and anthelmintic activity showed a dose-dependent efficacy in all the plants. H. japonicum showed the strongest anthelmintic activity with LC50 212.78 µg/mL followed by H. sibthorpioides (5.36 mg/mL), C. halicacabum (13.40 mg/mL), and A. scholaris (18.40 mg/mL). On the other hand, H. sibthorpioides showed stronger antiproliferative and apoptosis-inducing activity compared to other plants. The study observed a positive correlation between the antioxidant property and antiproliferative and anthelmintic activities of the plants. We, therefore, conclude that the secondary metabolites along with antioxidant molecules may have combined effects contributing the antiproliferative and anthelmintic activity of the plants.

All the plants and their secondary metabolites used in the present study were obtained from Ayurveda, with historical roots in the Indian subcontinent. The selected secondary metabolites have been experimentally validated and reported as potent antiviral agents against genetically-close human viruses. The plants have also been used as a folk medicine to treat cold, cough, asthma, bronchitis, and severe acute respiratory syndrome in India and across the globe since time immemorial. The present study aimed to assess the repurposing possibility of potent antiviral compounds with SARS-CoV-2 target proteins and also with host-specific receptor and activator protease that facilitates the viral entry into the host body. Molecular docking (MDc) was performed to study molecular affinities of antiviral compounds with aforesaid target proteins. The top-scoring conformations identified through docking analysis were further validated by 100 ns molecular dynamic (MD) simulation run. The stability of the conformation was studied in detail by investigating the binding free energy using MM-PBSA method. Finally, the binding affinities of all the compounds were also compared with a reference ligand, remdesivir, against the target protein RdRp. Additionally, pharmacophore features, 3D structure alignment of potent compounds and Bayesian machine learning model were also used to support the MDc and MD simulation. Overall, the study emphasized that curcumin possesses a strong binding ability with host-specific receptors, furin and ACE2. In contrast, gingerol has shown strong interactions with spike protein, and RdRp and quercetin with main protease (Mpro) of SARS-CoV-2. In fact, all these target proteins play an essential role in mediating viral replication, and therefore, compounds targeting aforesaid target proteins are expected to block the viral replication and transcription. Overall, gingerol, curcumin and quercetin own multitarget binding ability that can be used alone or in combination to enhance therapeutic efficacy against COVID-19. The obtained results encourage further in vitro and in vivo investigations and also support the traditional use of antiviral plants preventively.

Ethnobotanical relevance: Ficus racemosa L. is one of Assam's best-known plants with rich ethnomedicinal values. The Bodo population of Assam consumes the fruit extract from the plant as a preventative measure against diabetes.Aim of the study: The goal of this study was to investigate metal content, major phytocompounds, α-amylase and α-glucosidase inhibitory activity as well as cytotoxicity properties of Ficus racemosa fruit extracts.Materials and methods: The GC-MS technology was used to analyze the main phytochemical content of the plant and heavy metal detection was performed by Atomic absorption spectrophotometer. Enzyme inhibition was studied by UV/VIS spectrophotometric methods. Furthermore, the druglikeness and bioavailability properties of compounds were carried out using computer-aided tools, SwissADME and admetSAR. Docking and visualization were performed in AutoDock vina and Discovery studio. The latter research has been supported by the pharmacophore modeling and structure superimposition of studied compounds for lead molecules.Results: GC-MS analysis showed six major compounds from the plant. However, the study found that the fruits of Ficus racemosa contain negligible amounts of toxic elements. Biochemical studies found that the fruit of F. racemosa possesses strong α-amylase and α-glucosidase inhibitory properties. All the six compounds identified were predicted to have druglikeness property with high cell membrane permeability and bioavailability. The Docking study showed strong binding affinities between compounds and enzymes. At the same time in-vitro cytotoxicity and apoptosis results on healthy PBMC and splenocytes showed negligible toxicity (5-12%) after 24 h of exposure. Pharmacophore features and structure superimposition revealed compound 3 as a pivot moleculeConclusion: Ficus racemosa fruit extract inhibited α-amylase and α-glucosidase activity indicating its antihyperglycemic properties. Interestingly, negligible cytotoxic effect was seen in healthy PBMC and splenocytes.

Background: The use of medicinal plants for general wellbeing and disease treatment is a common practice among tribal communities of Kokrajhar districts of Assam. However, little works have been done to study the pharmacological aspect of the plants. Objectives: The present study intends to study the antioxidant and antiproliferative properties of selected medicinal plants used by the tribal communities of Kokrajhar district of Assam since ancient times. Methods: Five traditionally important medicinal plants namely, Cassia fistula, Citrus grandis, Lindernia crustacea, Sacciolepis myosuroides, and Zingiber zerumbet were investigated for antioxidant, antiproliferative (cytotoxic) and apoptosis-inducing potential in the malignant cancer cell line. Phytochemical content such as phenolic and flavonoid content were estimated following standard protocol. The methanolic extract of plants were investigated following phosphomolybdate method (TAC), FRAP, DPPH, ABTS, and TBARS assays. Antiproliferative activities of the plants were carried out by MTT assay in DL and PBMC cells. The apoptotic study was carried out following the acridine orange and ethidium bromide staining method and fluorescent microscopic imaging. Based on the significant (P≤0.05) high apoptotic inducing potential of the plant and to further dissect the molecular mode of action including downstream biological action, major phytochemicals derived from L. crustacea were investigated for its prospective binding affinity with antiapoptotic cancer target proteins. Results: Antioxidant studies by FRAP, DPPH, ABTS, and TBARS assay revealed that all the five plants contain considerable free radical scavenging activity. C. fistula showed the strongest free radical scavenging activity while the fruit peel extract of C. grandis showed poor activity. The overall antioxidant activities of plants such as TAC, FRAP, DPPH, ABTS, and TBARS may be arranged in decreasing activity as C. fistula > Z. zerumbet > L. crustacea > S. myosuroides > C. grandis. MTT based cell proliferation study showed that all the plants extract significantly (P≤0.05) inhibited cell viability with negligible cytotoxicity (~5-12%) in normal cells. Moreover, L. crustacea showed promising antiproliferative and apoptosis-inducing ability against Dalton’s lymphoma. It is worth mentioning that the major bioactive compounds of the most potent plant extract, L. crustacea interacted with anti-apoptotic proteins (cancer target) with higher affinity and the results are compared with reference inhibitors. Conclusion: It is worth noting that these plants have the potential to consider for further scientific studies in different cell lines and animal models. Furthermore, isolation and characterization of bioactive compound(s), may promise the discovery of new and valuable drugs candidate to tackle various human diseases.

Two new isostructural coordination compounds of Ni(II) and Mn(II) viz. [Ni(H2O)4(Hdmpz)2]ADS (1) and [Mn(H2O)4(Hdmpz)2]ADS (2) (where, Hdmpz = 3,5-dimethylpyrazole, ADS = anthraquinone-1,5-disulfonate) have been synthesized in aqueous medium at room temperature and characterized them using elemental analysis, TGA, FT-IR, electronic spectroscopy and single crystal X-ray diffraction techniques. Coordination compounds involving ADS anions in the crystal lattice are scarcely reported in the literature. Crystal structure analysis reveals the presence of unconventional O∙∙∙O dichalcogen bonding interaction between the O-atoms of neighbouring ADS moieties of the compounds. Aromatic π-stacking and unusual charge assisted O‒H∙∙∙O and C‒H∙∙∙O hydrogen bonds (CAHBs) are also involved in the stabilization of the crystal structures. Theoretical calculations have been performed to analyze the CAHBs, π-stacking and O∙∙∙O dichalcogen bonding interactions observed in the solid-state structures of 1 and 2 using DFT calculations, MEP surface analysis, QTAIM and NCI plot index computational tools. The relatively larger interaction energy observed for Ni(II) compound can be attributed to the higher contribution of the CAHBs than that for the Mn(II) complex. The energy associated to the O•••O dichalcogen bonding interaction is small (0.6 kcal/mol) and comparable with the weak C‒H•••O contact observed in compound 2. In vitro antiproliferative activities of the compounds considering cell cytotoxicity and apoptosis reveal the cytotoxic potential of the compounds in Dalton's Lymphoma (DL) cancer cells with negligible cytotoxicity in normal PBMC cells. Molecular docking simulation of the compounds with antiapoptotic proteins reveals significant affinity of the compounds with the active sites of the antiapoptotic proteins.

Two new Ni(II) coordination complexes involving fumarate and 1,10-phenathroline viz.; [Ni2(phen)2(µ-fum)(H2O)6](fum)·6H2O (1) and [Ni(phen)2(H2O)2](0.5 fum)(NO3)·4H2O (2) (fum = fumarate, phen = 1,10-phenanthroline) have been isolated in aqueous medium at room temperature. Crystal structure analyses of the compounds reveal the presence of cooperative (π–π)2/(π–π)1/(π–π)2 stacked ternary assemblies which provide stabilities to the layered architectures. The lattice water and the large counter anions in the lattice of the compounds are involved in the formation of unconventional discrete cyclic fumarate-water, fumarate-water-nitrate clusters and infinite nitrate-water 1D chains that are very scarcely reported in the literature. The energetically significant π-stacked dimers observed in the biologically relevant ternary assemblies of the crystal structures are further studied theoretically using DFT calculations and NCI plot index computational tools. DFT calculations reveal that the cooperative (π–π)2 binding mode of compound 1 is energetically more significant than (π–π)1 Moreover, the study also reveals that for the equivalent cooperative (π–π)1 stacking interactions in both the structures, the energy is unexpectedly higher for compound 2 than that observed for compound 1. Both the compounds induce significant cytotoxicity in Dalton's lymphoma (DL) cancer cells by inducing apoptotic cell death with negligible cytotoxicity in normal cells. Decrease in the mitochondrial membrane potential (MMP) of DL cells after treatment with the compounds also corroborates the apoptotic cell death. The molecular docking and pharmacophore features reveal that the compounds interact and accommodated well with the active sites of anti-apoptotic proteins.

Half-sandwich organometallic rhodium and iridium complexes [1–6] have been synthesized with ligands L1 (L1 = Pyridin-2-ylmethylene picolinichydrazine) and L2 (L2 = Pyridin-3-ylmethylene picolinichydrazine). Treatment of [{Cp∗MCl2}2] (M = Rh/Ir) with L1 in methanol has yielded mononuclear cationic complexes such as [{Cp∗M(L1N∩N)Cl}]PF6 where {M = Rh (1) and Ir (2)} and dinuclear complexes such as [{(Cp∗MCl)2(L1N∩N, N∩N)}]PF6 where {M = Rh (3) and Ir (4)} in 1:2 and 1:1 metal dimer to ligand ratios respectively. Reactions of [{Cp∗MCl2}2] with L2 in both 1:2 and 1:1 metal dimer to ligand ratios have yielded two metalla-macrocyclic dinuclear and dicationic complexes such as [{Cp∗M(L2N∩NμN)}2](PF6)2 where {M = Rh (5) and Ir (6)}. Spectroscopic and crystallographic data were used to elucidate the structures of the synthesized complexes. The in vitro antitumor evaluation of the complexes 1 and 2 by fluorescence based apoptosis study revealed their antitumor activity against Dalton’s ascites lymphoma (DL) cells. The antibacterial evaluation of complexes 1, 2, 5 and 6 by agar well-diffusion method revealed their significant activity against the two species considered viz., Proteus vulgaris (MTCC 426) and Vibrio parahaemolyticus (MTCC 451) with zone of inhibition up to 43 mm. The docking study with few key enzymes associated with cancer viz., ribonucleotide reductase, thymidylate synthase, thymidylate phosphorylase and topoisomerase II revealed their strong interactions with complexes under study. Complexes 1–6 exhibited a HOMO (highest occupied molecular orbital) – LUMO (lowest unoccupied molecular orbital) energy gap from 2.95 eV to 3.59 eV. TDDFT calculations explain the nature of electronic transitions and found well agreement with the experiments. Keywords: Rhodium dimer, Pyridin-2-ylmethylene picolinichydrazine, Metalla-macrocycles, Antitumor, Antibacterial, TDDFT

Two Ni(II) and Cu(II) coordination compounds viz. [Ni(phen)3](0.5adp)(2NO3)·4.5H2O (1) and [Cu4(phen)4(H2O)2(OH)4]4NO3·2H2O (2) (where, phen = 1,10-phenanthroline and adp = adipic acid) have been isolated in aqueous medium and characterized by single crystal XRD, TGA, elemental analysis and spectroscopic techniques (FT-IR and electronic). Crystal structure analysis of compound 1 reveals the unconventional enclathration of adp moieties in the tetrameric supramolecular host cavities via O(adp)···π and C–H···π interactions. The formation of discrete [(NO3)4(H2O)10]4− cores in 1 and unusual enclathration of the nitrate water clusters in the supramolecular host cavity of 2 provide additional reinforcement to the layered assemblies. DFT calculations and NCI plot computational tools have been employed to investigate the energetically significant enclathrated adp moieties in supramolecular host cavities of 1 and the antiparallel π-stacked ternary assemblies involving regium-π(chelate) interaction in 2. To the best of our knowledge, this is the first report of enclathration of adipic acid, a long chain aliphatic dicarboxylic acid; and non-covalent regium-π bonding interaction involving chelate ring in metal organic compounds. Finally, the compounds have been screened for in vitro antiproliferative activities in Dalton's Lymphoma (DL) cancer cell lines considering cell cytotoxicity, apoptosis and molecular docking. The compounds exhibit considerable cytotoxicity in DL cells with nominal effects in healthy normal PBMC cells. The docking study reveals the effective binding affinity of the compounds with the active sites of BCL family antiapoptotic proteins.

Two Mn(II) and Ni(II) coordination complexes viz. [Mn(phen)2(2,6-PDC)]·2CH3OH (1) and [Ni(2,6-PDC)2][Ni(H2O)4(en)]·6H2O (2) (phen = 1,10-phenanthroline, 2,6-PDC = 2,6-pyridinedicarboxylate and en = ethylenediamine) have been isolated at ambient conditions and characterized by elemental analysis, FT-IR, electronic spectroscopy, TGA and single crystal X-ray diffraction. Switching the solvent from methanol to water has changed the structural topologies of the compounds. Compound 1 is composed of a hepta-coordinated Mn(II) centre with two bidentate phen and one tridentate 2,6-PDC; whereas compound 2 is composed of cationic [Ni(H2O)4(en)]2+ and anionic [Ni(2,6-PDC)2]2– moieties with hexa-coordinated Ni(II) centers. Crystal structure analysis of compound 1 unfolds the presence of unorthodox O H(methanol)⋯π interactions involving the uncoordinated methanol molecules. The unusual enclathration of dual H-bonded guest (H2O)4 cores in the hexameric Ni(II) hosts in compound 2 provides rigidity to the crystal structure. The antiparallel π-stacked dimers and anti-cooperative HB···anion-π···HB assemblies observed in the solid-state structures of 1 and 2 respectively have been studied theoretically using DFT calculations and NCI plot index computational tools. In vitro anticancer evaluation of the compounds considering cell cytotoxicity and apoptosis assay showed significant concentration dependent cytotoxicity in Dalton’s lymphoma (DL) cancer cells with nominal effects in normal PBMC cells. To elucidate the possible mode of action of the cytotoxic behavior of the compounds, in silico docking studies have been carried out which revealed the efficient interaction of the compounds with the active sites of antiapototic cancer target proteins. The inhibitions of the activities of antiapoptotic target proteins have been further investigated using western blot analysis.

Two new benzoato bridged Mn(II) and Cu(II) dinuclear coordination compounds viz. [Mn2(bipy)2(4-Clbz)2(H2O)4]2(4-Clbz) (1) and [Cu2(bz)4(2-MePy)2] (2) (bipy = 2,2-bipyridine, 4-Clbz = 4-chlorobenzoate, bz = benzoate, 2-MePy = 2-methylpyridine) have been synthesized and characterized using elemental analysis, TGA, spectroscopic (FTIR, electronic, EPR) and single crystal X-ray diffraction techniques. Crystal structure analysis of compound 1 reveals the enclathration of guest 4-Clbz moiety in the supramolecular host tetramer which provides rigidity to the crystal structure. Further analysis reveals the presence of cooperative (π–π)2/(π–π)1/(π–π)2 ternary assemblies involving alternate coordinated and uncoordinated 4-Clbz moieties. In compound 2, intermolecular C H∙∙∙O, C H∙∙∙π and C H∙∙∙C contacts are involved in the formation of dimeric paddle wheel supramolecular assemblies which stabilizes the layered architecture. The cooperative interplay of H-bonding and π-stacked ternary assemblies of 1 has been studied theoretically using DFT calculations, MEP surface and NCI Plot computational tools. The large interaction energies along with the NCI plot index analysis confirm that the π-stacking assemblies in combination with the H-bonds are strong binding motifs. In vitro anticancer activity of the compounds considering cytotoxicity and apoptosis assays reveal significant concentration dependent cytotoxicity in Dalton's lymphoma (DL) cancer cell lines with nominal effects in normal healthy PBMC cells. Molecular docking study reveals the efficient interaction of the compounds with the antiapoptotic BCL family target proteins.

Two pyridinedicarboxylato bridged 1D coordination polymers of copper(II) viz.; {[Cu(2,5-PDC)(Hdmpz)2]·H2O}n (1) and {[Cu(2,3-PDC)]·10H2O}n (2) (where, Hdmpz = 3,5-dimethyl pyrazole, PDC = pyridinedicarboxylate) have been isolated and characterized using TGA, elemental analysis, spectroscopic (IR, electronic) and single crystal X-ray diffraction techniques. Crystal structure analysis of the compounds 1 and 2 reveals that unconventional C–H⋯π(carbonyl) and intramolecular O⋯C π-hole interactions provide stability to the crystal structures, respectively. Such C–H⋯π(carbonyl) and intramolecular O⋯C π-hole interactions are scarcely reported in the literature. Theoretical calculations have been performed to analyze the unconventional non-covalent interactions observed in the solid-state structures of 1 and 2 using NCI plot and QTAIM computational tools. We have also theoretically explored the semi-coordination (regium) Cu-Oaxial bonds present in the compound 2. The polymers have been further investigated for potential antiproliferative activities considering cell viability and apoptosis assays against Dalton’s lymphoma (DL) cancer cell lines and the results were compared with cisplatin (reference drug) in the same experimental conditions. The compounds significantly induce cytotoxicity in DL cells with nominal cytotoxicity in normal PBMC cells. The molecular doking simulation performed with the antiapoprotic protiens reveals strong binding affinities of the compounds with the active sites of the target proteins. To establish structure activity relationship (SAR), pharmacophore studies have been carried out to investigate the key pharmacophore features of the structures of the compounds responsible for biological activities.

Two new coordination compounds viz. [Ni(phen)2(NO3)](NO3)·4H2O (1) and [Ni(phen)2(H2O)Cl]Cl·4H2O (2) (phen = 1,10-phenanthroline) have been synthesized and characterized using elemental analysis, TGA, PXRD, electronic, FT-IR spectroscopy and single crystal X-ray diffraction techniques. Crystal structure analysis reveals the formation of discrete water and anion-water clusters that contribute to the layered assemblies of the compounds. Moreover, the enclathration of (H2O)4 cluster in the layered assembly of 2 also provides rigidity to the crystal structure. Unconventional anion-π interaction is also observed in compound 1 involving the π-system of the chelate ring of coordinated phen. Detailed structural investigation reveals the presence of biologically relevant cooperative π-stacked (π–π)1/(π–π)2/(π–π)1 ternary assemblies in both the compounds. Interestingly, DFT calculations reveal that (π-π)2 binding mode in 2 is energetically significant than in compound 1 which is further analyzed by NCI plot index computational tool. The compounds have been screened for anticancer activities considering cell cytotoxicity and apoptosis in Dalton's lymphoma (DL) malignant cancer cell line. The complexes significantly inhibit cell viability by inducing apoptotic cell death in cancer cell lines with negligible cytotoxicity in normal cells. DNA ladder assay results in the degradation of genomic DNA into small inter-nucleosomal fragments (damage DNA) which is a biochemical hallmark of DL cells undergoing apoptosis. Lactate dehydrogenase (LDH) leakage assay also reveals the release of the intracellular enzyme LDH from DL cells indicating the irreversible cell death involving cell membrane damage. The molecular docking simulations reveal that the compounds interact and accommodated well with the active site of anti-apoptotic BCL proteins. Structure activity relationship (SAR) analysis based on pharmacophore modelling reveal that the molecular features of the compounds play important roles in the biological activities.

Two new coordination compounds of Ni(II) and Cu(II), viz. [Ni(phen)2Cl(H2O)] 4-NO2bz·3H2O (1) and [Cu(phen)2Cl]Cl·5H2O (2) (phen = 1,10-phenanthroline, 4-NO2bz = 4-nitrobenzoate) have been synthesized and characterized by single crystal X-ray diffraction, elemental analysis, FT-IR, electronic spectroscopy, TGA and EPR. The detailed crystal structure analysis of the Werner Type Clathrate 1 reveals the self-assembled unconventional enclathration of 4-NO2bz moieties in supramolecular Ni(II) hosts. In addition to the conventional discrete (H2O)n clusters in the crystal structure of 2, the layered architecture involves enclathration of single guest water molecules in the Cu(II) supramolecular hosts. We have theoretically analysed the biologically relevant anti-parallel π-stacking interactions in compound 1 and two types of anion–π interactions involving coordinated and uncoordinated chloride ions in compound 2. MEP surface analysis and DFT calculations reveal that the anti-parallel π-stacking interaction in 1 is energetically significant and enhanced upon complexation of the ligands to the Ni(II) centre. Remarkably, studies also reveal that in addition to the conventional anion⋯π interaction involving the chloride anion in the lattice, the unusual Cl(chlorido)⋯π interaction observed in the crystal assembly of 2 is also energetically significant. The antiproliferative potential of the compounds 1 and 2 have been studied in Dalton’s Lymphoma (DL) malignant cancer cell lines considering MTT cell viability and apoptosis assays. The compounds 1 and 2 exhibited significant concentration dependent increase in cell cytotoxicity and apoptosis in DL cells with negligible cytotoxicity in normal (PBMC) cells.

Two new coordination compounds viz. [Ni(2,6-PDC)(Hdmpz)(H2O)2]∙H2O (1) and [Zn(3-CNpy)2Cl2] (2) (2,6-PDC = 2,6-pyridinedicarboxylate, Hdmpz = 3,5-dimethylpyrazole, 3-CNpy = 3-cyanopyridine) have been synthesized and characterized using elemental analysis, thermogravimetric analysis, electronic, infrared spectroscopy and single crystal X-ray diffraction techniques. Crystal structure analyses reveal the presence of supramolecular assemblies involving interesting dimers with unconventional contacts in the compounds. DFT (Density Functional Theory) calculations on the supramolecular dimers in the crystal structure of 1 reveal that the sum of contributions of anion–π, π–π and other long range interactions due to the approximation of the bulk monomers is energetically significant. Molecular Electrostatic Potential (MEP) surface and Quantum Theory of Atoms in Molecules (QTAIM) analyses on the interesting supramolecular dimers of the crystal structures of 2 reveal the presence of unconventional anion⋯π contacts involving coordinated chlorido ligands and C–H⋯π(nitrile) interactions involving the π-system of the nitrile moiety of 3-cyanopyridine. Remarkably, Atoms in Molecules analysis also confirms the existence of energetically significant unconventional anti-parallel nitrile⋯nitrile interaction in the crystal structure of 2. Cell cytotoxicity of the compounds performed in Dalton's lymphoma (DL) malignant cancer cell line showed effective potency with negligible cytotoxicity in normal cells (~12%). It is interesting that compound 1has excellent cytotoxic potency with IC50 closer to cisplatin and can bind different biological targets with similar signalling pathways. Structure activity relationship (SAR) analyses of 1 and 2 based on pharmacophore modelling reveal that the molecular features associated with the structures of the compounds play important role in the biological activities.

Two new isostructural coordination compounds of cobalt(II) and zinc(II) involving 2,2′-bipyridine and 2,5-pyridine dicarboxylate, viz. [Co(2,5-PDC)(bipy)2]·7H2O (1) and [Zn(2,5-PDC)(bipy)2]·7H2O (2) (bipy = 2,2′-bipyridine and 2,5-PDC = 2,5-pyridine dicarboxylate), have been synthesized in purely aqueous medium at room temperature. The compounds have been further characterized by single crystal X-ray diffraction, FT-IR, electronic spectroscopy, thermal and elemental analysis. Several non-covalent interactions, such as C H⋯O and anti-parallel π-stacking contacts, build up the supramolecular layered architectures of the crystal structures. Further analysis of the crystal structures reveals the self-assembled enclathration of a 1D H-bonded (H2O)8 chain into the supramolecular hexameric host cavity which brings rigidity to the crystal structures. Such unconventional enclathration of H-bonded water molecules in a metal–organic supramolecular host involving bipy is scarcely described in the literature. We have theoretically evaluated the strength of the anti-parallel π-stacking interactions that are crucial for the stabilization of the supramolecular dimers of the compounds. The influences of the metal coordination on the strength of the π-stacking interactions have been confirmed using DFT calculations and NCI plot computational tools. The antiproliferative activities of the compounds have been investigated in the DL cell line using MTT cell viability and apoptosis assays. The compounds significantly induce concentration dependent cell cytotoxicity and apoptosis in DL cells with negligible cytotoxicity in normal (PBMC) cells. A molecular docking study also reveals a strong interaction of the compounds with the active site of anti-apoptotic BCL proteins. Pharmacophore features of the structures of the compounds responsible for the biological activities were also generated to establish a structure activity relationship (SAR).

Three new coordination compounds of types [Co(py)(2,6-PDC)(H2O)2].H2O (1), [Ni(py)(2,6-PDC)(H2O)2].H2O (2) and [Cu(py)(2,6-PDC)(H2O)].2H2O (3) (py = pyridine, 2,6-PDC = Pyridine-2,6-dicarboxylate) have been synthesized from purely aqueous media and characterized using elemental analysis, spectroscopic (IR and electronic) and single crystal X-ray diffraction techniques. Several supramolecular contacts of types O H⋯O, C H⋯O, C H⋯π, C H⋯C and π–π stacking stabilize the crystal structures. The layers in the crystal structures stack in perpendicular direction resulting in 1D channel with enclathrated water molecules. The strength of the antiparallel π-stacking interactions involving the pyridine rings in the supramolecular dimer of the compounds have been evaluated using DFT calculations and the influence of the pyridine coordination to the strength of the stacking assembly have been confirmed. The anti-proliferative potential of the compounds has been studied in Dalton’s lymphoma (DL) cell line by using MTT cell viability assay and apoptosis assay. All the three complexes exhibit short term (24 h) cytotoxicity (∼20–30%) through apoptotic cell death with negligible cytotoxicity (∼5–10%) in normal cells. In silico docking simulation has been performed with apoptosis regulator protein BCL-2 for the identification of possible molecular mode of action of the synthesized complexes. The pharmacophore features based on structure activity relationship (SAR) of the complexes have been identified. The SAR results reveal that the molecular features such as, hydrophobic, aromatic, positive ionizable, negative ionizable, H-bond donor and acceptor and halogen bond donor associated with the structures of the compounds play important role in the biological activities. The ADMET features, viz., physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness of the synthesized complexes have been investigated.

A new coordination polymer of nickel(II) involving bridging fumarato viz. catena[μ-fumarato(1,10-phenanthroline monohydrate(diaqua))nickel(II)trihydrate], {[Ni(μ-fum)(phen)(H2O)2].3H2O}n (1) (where, fum = fumarate, phen = 1,10-phenanthroline monohydrate) has been synthesized in purely aqueous medium at room temperature. The crystal structure of the polymer has been determined by single crystal X-ray Diffraction analysis. The polymer has been characterised by FT-IR, electronic spectroscopy, thermal and elemental analysis. The zig-zag polymeric chain of 1 self assembles into 2D supramolecular network architecture via reciprocal π-π stacking interactions. The lattice water molecules are involved in the formation of unique supramolecular octameric linear water clusters involving alternate trimeric rings that stabilizes the 2D network architecture. The crystal structure of the polymer also reveals the self-assembled enclathration of (H2O)8 cluster into polymeric Ni(II) host involving fum ligands that brings rigidity to the structure. Theoretical calculations have been performed to analyse the non-covalent interactions observed in the solid-state structure of 1. In particular, we have analysed the π–π stacking interactions between the phen ligands and also the energetically significant unconventional O H⋯π interaction involving the π-system of fum. For the latter, we have investigated the ability of the double bond of fum (coordinated to Ni) to establish O H⋯π interaction with water in comparison to fum acid and simple ethene. Finally, the polymer has been investigated for potential anticancer activities considering cell cytotoxicity, apoptosis and molecular docking as a major parameters against Dalton’s lymphoma (DL) malignant cancer cell line and the results were compared with cisplatin (reference drug) under the same experimental conditions. DNA interaction and fragmentations have been investigated for compound 1 and pharmacophore features establish structure activity relationship (SAR).

Three new isostructural coordination solids viz. [Co(3-CNpy)2(2-ClBz)2(H2O)2] (1), [Mn(3-CNpy)2(2-ClBz)2(H2O)2] (2) and [Zn(3-CNpy)2(2-ClBz)2(H2O)2] (3) (3-CNpy = 3-cyanopyridine, 2-ClBz = 2-chlorobenzoate) have been synthesized from purely aqueous media and characterized by X-ray crystal structure analysis, FT-IR, electronic spectra and TGA. Several non-covalent hydrogen bonding interactions of the types O H⋯O, C H⋯O, C H⋯N, C H⋯Cl and π-π stacking contacts build up the supramolecular networks in the crystal structures. Electrostatically enhanced π-π interactions are observed in 1–3 between the phenyl rings of 2-ClBz and pyridine ring of 3-CNpy of the monomeric units of the complexes. We have used the molecular DFT calculations to evaluate energetically the strength of these contacts and also to analyze the effect of the metal on the interaction energies. The energetic features of the H-bonding and π-stacking interactions for 1–3 reveal that the H-bonded assembly is more favorable than the π-stacked contacts. The electrostatically enhanced energy of the π-stacking interactions is stronger than that usually observed for π-stacking interactions involving arenes. The cytostatic potential of all complexes have been studied in Dalton’s lymphoma (DL) cell line by MTT assay, apoptosis assay and further corroborated with molecular docking simulation. The complexes exhibit cytotoxicity (∼25–30%) through apoptotic cell death with negligible cytotoxicity (∼5–10%) in normal PBMC cells. In silico-docking techniques have been performed with apoptosis regulator protein BCL-2 for the identification of critical amino acids and their possible binding affinity with the synthesized complexes. The pharmacophore features based on structure activity relationship (SAR) of the complexes have been identified and the study reveal that the features viz., hydrophobic, aromatic, positive ionizable, negative ionizable, H-bond donor and acceptor and halogen bond donor properties play important role for the biological activities of the complexes.

BACKGROUND Esophageal squamous cell carcinoma (ESCC) is a common cancer in the north east of India. The present study concerned the prevalence of human papilloma virus (HPV) in the ESCC in north eastern India and its impact on response to chemotherapy. MATERIALS AND METHODS p16 expression, a surrogate marker for HPV infection was assessed in 101 pre-treatment biopsies of locally advanced ESCC, reported from a comprehensive cancer centre in north east India, using immunohistochemistry. All patients received neo-adjuvant chemotherapy. Response was assessed clinically and histopathologically with attention to p16 expression. RESULTS p16 was expressed in 22% of ESCC (22 out of 101) and was more prevalent in patients who were more than 45 years of age (P=0.048). p16 positive tumors appeared more commonly in the upper 2/3 of the thoracic esophagus (18 in 22). Nine of the 22 (41%) p16 positive tumors achieved pathologic complete response following neo-adjuvant chemotherapy (P=0.008). There was a trend towards reduced mortality in this group (P=0.048). Some 9 of the 20 (45%) patients who achieved pathologic complete response were p16 positive. CONCLUSIONS Expression of p16 in ESCC correlates with higher rate of pathologic complete remission in patients undergoing neo adjuvant chemotherapy and could be a predictive marker for response assessment.

Two new coordination complexes viz. [Mn2(μ‑O,O′‑4‑Mebz)2(bpy)2(μ2‑H2O)(4‑Mebz)2] (1) and [Zn(bpy)(pdc)(H2O)]·3.5H2O (2) (where bpy = 2,2′‑bipyridine, 4‑Mebz = 4‑methyl benzoate and pdc = 2,6‑pyridine dicarboxylate) were synthesized and structurally characterized by single crystal X-ray diffraction, FT-IR, electronic spectroscopy, Thermogravimetric Analysis (TGA) and Powder X-ray diffraction (PXRD) techniques. Complex 1 consists of a dinuclear Mn(II) unit bridged by a solvent water molecule while 2 is a mononuclear complex. The supramolecular assemblies found in the solid state of both complexes have been described. In 2, several π-stacking interactions modes have been further studied using Density Functional Theory (DFT) calculations. Furthermore, the activity of the complexes against a few pathogenic bacteria has been studied and confirmed. Finally, the antiproliferative activities of both complexes have been studied in T-cell lymphoma cell line by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, apoptosis assay and molecular docking simulation. Both the complexes exhibit gratifying cytotoxicity through apoptotic cell death with negligible cytotoxicity (~5–10%) in normal cells. It is worth mentioning that Mn(II) and Zn(II) complexes exhibit interaction modes with highly expressed cancer target proteins under study with higher binding affinity and the results are comparable with reference inhibitors.

Objective: To obtain suitable artimisinin-based drug candidates with high antimalarial activity. Methods: Three different reaction schemes were used to synthesize a total of 15 artemisinin-based compounds. The first synthetic scheme involved the synthesis of diazido aliphatic and aromatic compounds from commercially available dihalides and azido derivatives of artemisinin. The second scheme consisted of the reaction of dibromoaliphatic compounds with sodium azide in dimethylformamide which yielded the desired compounds. Artemisinin-based compounds on treatment with sodium azide and bromotrimethylsilane in dichloromethane produced the most potent compound GB-2. Another potent compound GB-1 was synthesized from artemisinin by treatment with alcohols in the presence of Aberlyst-15 in anhydrous dichloromethane. The third scheme involved the Huisgen 1,3-dipolar cycloaddition between the synthesized aliphatic and aromatic diazides and two alkyne derivatives of artemisinin to obtain the desired artemisinin dimers with average yields. Results: The best in vitro antiplasmodial activity was shown by the compound GB-2 registering IC50 value 0.066 μg/mL against chloroquine-sensitive and 0.865 μg/mL against chloroquine-resistant strains of Plasmodium falciparum. It suppressed 59.0% parasitaemia in vivo of rodent malaria parasite Plasmodium berghei in Swiss albino model at 50 μg/kg body weight dosage. Molecular docking interactions of Plasmodium falciparum ATP6 (PfATP6) protein revealed strong bonding of GB-2 with Thr255 residue which is likely to be the reason for excellent antimalarial activity of this compound. Conclusion: Two compounds GB-1 and GB-2 exhibited excellent in vitro antiplasmodial activity and fair in vivo antimalarial activity. Of the two, GB-2 showed better activity which could be attributed to its strong bonding interactions with Thr255 as evidenced from the molecular docking study. Study helped in identifying artemisinin analogues possessing good antimalarial properties and further research in structural alterations of the selected molecules should be carried out which may result in obtaining potent drug candidates against the malarial parasite.

Phosphoenolpyruvate carboxykinase (PEPCK), a carboxylase enzyme is present in all living organisms. It catalyzes metal-nucleotide coupled reversible decarboxylation and phosphorylation between phosphoenolpyruvate (PEP) and oxaloacetate (OAA) depending on the system and the availability of the intermediates. In fungi, plants and in most bacteria, production of PEP from OAA by PEPCK is the key step during gluconeogenesis. In healthy human cytosolic PEPCK enzyme is present only during glucose starvation; cytosolic PEPCK rapidly disappears on the replenishment of glucose due to hormonal control of the transcription of the cytosolic PEPCK- gene. In some parasitic helminthes like Ascaris suum, nematodes such as Haemonchus contortus, PEPCK carry out the reverse reaction to produce OAA from PEP. In Trypanosoma cruzi and all species of the genus Leishmania, this enzyme is very active even in the presence of high level of carbohydrate. There is a significant functional difference between parasitic PEPCK and mammalian host PEPCK. These differences between the mammalian host and the parasite enzyme strongly support the belief that PEPCK should be further investigated as a possible target for selective chemotherapeutic agents. The experimental 3D structure of PEPCK of Schistosoma japonicum is not available in protein data bank. Therefore, based on the knowledge of the best template (3DT7), model of 3D structure of Schistosoma japonicum PEPCK was prepared using Modeller v9.10 software and processed in to energy minimization, Ramachandran plot analysis, quality assessment and characterization.

Phosphoenolpyruvate carboxykinase (PEPCK) is an important catalytic enzyme in helminth parasites that catalyses a reverse reaction forming oxaloacetate from phosphoenolpyruvate. Because of its functional significance, present work was undertaken to construct and validate the 3D structure of PEPCK in Schistosoma mansoni. The 3D model protein was generated based on the known crystal structure of rat cytosolic PEPCK as template using Modeller 9v10 software. The resulting models were assessed by Procheck, Anolea, ProSA-web, and Errat. We have also identified all the pockets and voids on the best model protein to provide a detailed delineation of all atoms participating in their formation using CASTp server and to dock with best fitted ligand (guanosine diphosphate, GDP) using AutoDock 4.2. The model protein showed reliable structure with Ramachandran plot: 90.2 % core region, 9.1 % allow, 0.8 % generously allowed and 0.0 % disallowed region amino acid distributions. GDP was found to be docked in its active site, which formed a single H-bond with ASN 524 residue of model protein. Characterisation of PEPCK model protein has also been done to know its various biochemical natures. Therefore, the model structure could prove useful in further functional characterization and may be used to target and design drugs against S. mansoni.

Southeast Asia, especially India, is well known for the highest use of smokeless tobacco. These products are known to induce oral squamous cell carcinoma. However, not all long-term tobacco-chewers develop oral squamous cell carcinoma. In addition, germline variants play a crucial role in susceptibility, prognosis, development, and progression of the disease. These prompted us to study the genetic susceptibility to oral squamous cell carcinoma among the long-term tobacco-chewers. Here, we presented a retrospective study on prolonged tobacco-chewers of Northeast India to identify the potential protective or risk-associated germline variants in tobacco-related oral squamous cell carcinoma along with HPV infection. Targeted re-sequencing (n = 60) of 170 genetic regions from 75 genes was carried out in Ion-PGM™ and validation (n = 116) of the observed variants was done using Sequenom iPLEX MassARRAY™ platform followed by polymerase chain reaction–based HPV genotyping and p16-immunohistochemistry study. Subsequently, estimation of population structure, different statistical and in silico approaches were undertaken. We identified one nonsense-mediated mRNA decay transcript variant in the DFNA5 region (rs2237306), associated with Benzo(a)pyrene, as a protective factor (odds ratio = 0.33; p = 0.009) and four harmful (odds ratio > 2.5; p

Reaction of salicylaldehyde-2-picolinylhydrazone (HL) Schiff base ligand with precursor compounds [{(p-cymene)RuCl2}2] 1, [{(C6H6)RuCl2}2] 2, [{Cp*RhCl2}2] 3 and [{Cp*IrCl2}2] 4 yielded the corresponding neutral mononuclear compounds 5-8, respectively. The in vitro antitumor evaluation of the compounds 1-8 against Dalton's ascites lymphoma (DL) cells by fluorescence-based apoptosis study and by their half-maximal inhibitory concentration (IC50) values revealed the high antitumor activity of compounds 3, 4, 5 and 6. Compounds 1-8 render comparatively lower apoptotic effect than that of cisplatin on model non-tumor cells, i.e., peripheral blood mononuclear cells (PBMC). The antibacterial evaluation of compounds 5-8 by agar well-diffusion method revealed that compound 6 is significantly effective against all the eight bacterial species considered with zone of inhibition up to 35 mm. Fluorescence imaging study of compounds 5-8 with plasmid circular DNA (pcDNA) and HeLa RNA demonstrated their fluorescence imaging property upon binding with nucleic acids. The docking study with some key enzymes associated with the propagation of cancer such as ribonucleotide reductase, thymidylate synthase, thymidylate phosphorylase and topoisomerase II revealed strong interactions between proteins and compounds 5-8. Conformational analysis by density functional theory (DFT) study has corroborated our experimental observation of the N, N binding mode of ligand. Compounds 5-8 exhibited a HOMO (highest occupied molecular orbital)-LUMO (lowest unoccupied molecular orbital) energy gap 2.99-3.04 eV. Half-sandwich ruthenium, rhodium and iridium compounds were obtained by treatment of metal precursors with salicylaldehyde-2-picolinylhydrazone (HL) by in situ metal-mediated deprotonation of the ligand. Compounds under investigation have shown potential antitumor, antibacterial and fluorescence imaging properties. Arene ruthenium compounds exhibited higher activity compared to that of Cp*Rh/Cp*Ir in inhibiting the cancer cells growth and pathogenic bacteria. At a concentration 100 µg/mL, the apoptosis activity of arene ruthenium compounds, 5 and 6 (~30 %) is double to that of Cp*Rh/Cp*Ir compounds, 7 and 8 (~12 %). Among the four new compounds 5-8, the benzene ruthenium compound, i.e., compound 6 is significantly effective against the pathogenic bacteria under investigation.

Background: The prevalence of locally advanced esophageal squamous cell carcinoma (ESCC) remains high despite technological advancements in its diagnosis. This leads to prolonged multimodality treatment often resulting in poor response eventually leading to poor prognosis. Currently, there are no biomarkers available to predict response to neoadjuvant chemotherpy. Aldehyde dehydrogenase 1 (ALDH1), human epidermal growth factor receptor-2 (HER2), p16INK4A, ploidy and S phase fraction are considered significant biomarkers in various solid malignancies. However, there is paucity of data on their clinical significance in ESCC. In the present study, we investigated their significance in predicting the response to neoadjuvant chemotherapy (NACT) in ESCC patients. Methods: Immunohistochemisty of ALDH1, HER2, p16INK4A and propidium iodide based cell cycle analysis through flow cytometer was performed in pre treatment biopsy sample collected from 108 ESCC patients who were presented at a comprehensive cancer centre in northeast India and all of them subsequently received neo adjuvant chemotherapy. Results: ALDH 1, HER2 and p16INK4A were found positive in 65.7%, 7.4% and 22% of pre treatment ESCC specimens respectively. ALDH1 expression correlates with poor response to neo adjuvant chemotherapy (P Citation Format: Rajeev Kumar, R. Ravi Kannan, Akalesh Kumar Verma, Anuradha Talukdar, Monoj Kumar Deka, Ritesh Tapkire, Litika Vermani, Sankar Kumar Ghosh. High ALDH1, S phase fraction, p16INK4A in esophageal squamous cell carcinoma could predict response to neoadjuvant chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2788. doi:10.1158/1538-7445.AM2017-2788

Cantharidin, a type of terpenoid, is the blistering agent of blister beetles frequently used in traditional medicine. The isolation and anticancer activity of cantharidin from blister beetles,Mylabris cichoriihas been recently reported by us. This study deals with changes in mitochondrial structure and function and understanding their significance in the underlying mechanism(s) in cantharidin-mediated antitumor effects in Dalton's lymphoma (DL) bearing mice. Cantharidin treatment caused the appearance of abnormal mitochondrial features which included roundish mitochondria with thickened membranes, irregularity in cristae, and appearance of small and large size vacuoles in mitochondria of DL cells. Cantharidin treatment resulted in a decrease in mitochondrial reduced glutathione, succinate dehydrogenase activity, mitochondrial membrane potential, and induced apoptosis and necrosis in DL cells. The decrease/release of mitochondrial cytochrome c were also observed after cantharidin treatment. Flow cytometry-based cell cycle analysis showed a time-dependent accumulation of the sub-G0 population of DL cells, thus, confirming the involvement of apoptosis in tumor cells in cantharidin-mediated antitumor activity. These finding signify that the apoptosis induced by cantharidin in DL cells should involve mitochondrial-dependent pathways. It is suggested that these cantharidin-mediated changes in mitochondria may play a crucial role in its antitumor activity.

Half‐sandwich ruthenium, rhodium and iridium complexes (1–12) were synthesised with aldoxime (L1), ketoxime (L2) and amidoxime (L3) ligands. Ligands have the general formula [PyC(R)NOH], where R = H (L1), R = CH3 (L2) and R = NH2 (L3). Reaction of [{(arene)MCl2}2] (arene = p‐cymene, benzene, Cp*; M = Ru, Rh, Ir) with ligands L1–L3 in 1:2 metal precursor‐to‐ligand ratio yielded complexes such as [{(arena)MLκ2(N∩N)Cl}]PF6. All the ligands act as bidentate chelating nitrogen donors in κ2 (N∩N) fashion while forming complexes. In vitro anti‐tumour activity of complexes 2 and 10 against HT‐29 (human colorectal cancer), BE (human colorectal cancer) and MIA PaCa‐2 (human pancreatic cancer) cell lines and non‐cancer cell line ARPE‐19 (human retinal epithelial cells) revealed a comparable activity although complex 2 demonstrated greater selectivity for MIA PaCa‐2 cells than cisplatin. Further studies demonstrated that complexes 3, 6, 9 and 12 induced significant apoptosis in Dalton's ascites lymphoma (DL) cells. In vivo anti‐tumour activity of complex 2 on DL‐bearing mice revealed a statistically significant anti tumour activity (P = 0.0052). Complexes 1–12 exhibit HOMO–LUMO energy gaps from 3.31 to 3.68 eV. Time‐dependent density functional theory calculations explain the nature of electronic transitions and were in good agreement with experiments.

Ethnopharmacological importance The blister beetles Epicauta hirticornis and Mylabris cichorii are used as a folk medicine by the Karbi tribe in Karbi Anglong district of Assam, India for the treatment of different human ailments, including cancer cases. Aim of the study It includes field survey related to zoo-therapeutic aspects of two blister beetles in Karbi community, isolation of bio-active compound and evaluation of its antitumor potential with possible mode of action against murine Ehrlich ascites carcinoma (EAC). Materials and methods The main bio-active compound of blister beetles was isolated from ethyl acetate extract and the structure was confirmed as cantharidin using NMR, IR, Mass and X-ray diffractometer. The effect of cantharidin on apoptosis, necrosis, autophagy and the apoptosis related signaling pathways were determined using different bioassays, including cell cycle analysis, mitochondrial membrane potential, western blot analysis of cytochrome c, caspases 9, 3/7 assays, and lactate dehydrogenase (LDH) assay. Results Cantharidin induced apoptosis, necrosis and autophagy cell death in EAC cells. The decrease in mitochondrial membrane potential was observed, which may help to release cytochrome c from mitochondria to cytosol. Cantharidin treatment caused up-regulation of caspases 9 and −3/7 and a decrease in LDH activity in EAC cells. Conclusion The major bioactive compound of these blister beetles is cantharidin which induces severe apoptosis in EAC cells involving mitochondrial intrinsic pathway. Cantharidin-mediated inhibition of LDH activity may lead to short supply of NAD+ and cut off energy and anabolic supply to cancer cells.