Search

Abstract Herein we have reported a fluorescent probe (MB-M) based on MB derivative for Cu2+ ions detection. The probe was well characterized by 1H NMR, 13C NMR and HR-MS spectrum. Probe MB-M showed naked-eyes recognition to Cu2+ as color change from colorless to indigo. The probe exhibited promising features such as high fluorescence and UV–vis selectivity, fast response (5 mint), workable at pH 2–7, and low limit of detection (LOD = 0.33 µM). Probe MB-M was also used for Cu2+ ions imaging in HepG-2 cells and detection in daily life (Test Strip and lake water). Moreover, non-covalent interaction (NCI) and quantum theory of atoms in molecules (QTAIM) analysis were used to study the interaction between MB-M and Cu2+ ions. By examining the electronic characteristics of the complex using natural bond orbital (NBO), electron density difference (EDD), and frontier molecular orbital (FMO) analysis, the sensitivity of MB-M towards Cu2+ ions were investigated. The results illustrated that the interactions between MB-M and Cu2+ ions involved chemisorption.

Abstract The COVID-19 has had a significant influence on people's lives across the world. The viral genome has undergone numerous unanticipated changes that have given rise to new varieties, raising alarm on a global scale. Bioactive phytochemicals derived from nature and synthetic sources possess lot of potential as pathogenic virus inhibitors. The goal of the recent study is to report new inhibitors of Schiff bases of 1,3-dipheny urea derivatives against SARS COV-2 spike protein through in-vitro and in-silico approach. Total 14 compounds were evaluated, surprisingly, all the compounds showed strong inhibition with inhibitory values between 79.60% and 96.00% inhibition. Here, compounds 3a (96.00%), 3d (89.60%), 3e (84.30%), 3f (86.20%), 3g (88.30%), 3h (86.80%), 3k (82.10%), 3l (90.10%), 3m (93.49%), 3n (85.64%), and 3o (81.79%) exhibited high inhibitory potential against SARS COV-2 spike protein. While 3c also showed significant inhibitory potential with 79.60% inhibition. The molecular docking of these compounds revealed excellent fitting of molecules in the spike protein receptor binding domain (RBD) with good interactions with the key residues of RBD and docking scores ranging from − 4.73 to − 5.60 kcal/mol. Furthermore, molecular dynamics simulation for 150 ns indicated a strong stability of a complex 3a:6MOJ. These findings obtained from the in-vitro and in-silico study reflect higher potency of the Schiff bases of 1,3-diphenyl urea derivatives. Furthermore, also highlight their medicinal importance for the treatment of SARS COV-2 infection. Therefore, these small molecules could be a possible drug candidate.

Abstract Diabetes mellitus has a high prevalence rate and it has been deemed a severe chronic metabolic disorder with long-term complications. This research aimed to identify compounds that could potentially inhibit the vital metabolic enzyme α-glucosidase and thereby exert an anti-hyperglycemic effect. The main goal was to establish an effective approach to control diabetes. To proceed with this study, a series of novel coumarin-derived thiosemicarbazones 3a–3m was synthesized and examined using a variety of spectroscopic methods. Moreover, all the compounds were subjected to α-glucosidase inhibition bioassay to evaluate their antidiabetic potential. Fortunately, all the compounds exhibited several folds potent α-glucosidase inhibitory activities with IC50 values ranging from 2.33 to 22.11 µM, in comparison to the standard drug acarbose (IC50 = 873.34 ± 1.67 µM). The kinetic studies of compound 3c displayed concentration-dependent inhibition. Furthermore, the binding modes of these molecules were elucidated through a molecular docking strategy which depicted that the thiosemicarbazide moiety of these molecules plays a significant role in the interaction with different residues of the α-glucosidase enzyme. However, their conformational difference is responsible for their varied inhibitory potential. The molecular dynamics simulations suggested that the top-ranked compounds (3c, 3g and 3i) have a substantial effect on the protein dynamics which alter the protein function and have stable attachment in the protein active pocket. The findings suggest that these molecules have the potential to be investigated further as novel antidiabetic medications.

In the original publication [...]

Abstract Cancer is one of the leading causes of death worldwide. The increasing prevalence and resistance to chemotherapy is responsible for driving the search of novel molecules to combat this disease. In search of novel compounds with pro-apoptotic potential, pyrazolo-pyridine and pyrazolo-naphthyridine derivatives were investigated against cervical cancer (HeLa) and breast cancer (MCF-7) cells. The anti-proliferative activity was determined through the MTT assay. Potent compounds were then analyzed for their cytotoxic and apoptotic activity through a lactate dehydrogenase assay and fluorescence microscopy after propidium iodide and DAPI staining. Flow cytometry was used to determine cell cycle arrest in treated cells and pro-apoptotic effect was verified through measurement of mitochondrial membrane potential and activation of caspases. Compounds 5j and 5k were found to be most active against HeLa and MCF-7 cells, respectively. G0/G1 cell cycle arrest was observed in treated cancer cells. Morphological features of apoptosis were also confirmed, and an increased oxidative stress indicated the involvement of reactive oxygen species in apoptosis. The compound-DNA interaction studies demonstrated an intercalative mode of binding and the comet assay confirmed the DNA damaging effects. Finally, potent compounds demonstrated a decrease in mitochondrial membrane potential and increased levels of activated caspase-9 and -3/7 confirmed the induction of apoptosis in treated HeLa and MCF-7 cells. The present work concludes that the active compounds 5j and 5k may be used as lead candidates for the development of lead drug molecules against cervical and breast cancer.

Abstract Type II diabetes mellitus (T2DM) is a global health issue with high rate of prevalence. The inhibition of α-glucosidase enzyme has prime importance in the management of T2DM. This study was established to synthesize Schiff bases of 1,3-dipheny urea (3a–y) and to investigate their in vitro anti-diabetic capability via inhibiting α-glucosidase, a key player in the catabolism of carbohydrates. The structures of all compounds were confirmed through various techniques including, Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) and mass-spectrometry (MS) methods. Interestingly all these compounds displayed potent inhibition IC50 values in range of 2.14–115 µM as compared to acarbose used as control. Additionally, all the compounds were docked at the active site of α-glucosidase to predict their mode of binding. The docking results indicates that Glu277 and Asn350 play important role in the stabilization of these compounds in the active site of enzyme. These molecules showed excellent predicted pharmacokinetics, physicochemical and drug-likeness profile. The anti-diabetic potential of these molecules signifies their medical importance and provide insights into prospective therapeutic options for the treatment of T2DM.

Abstract Here, we report the synthesis, carbonic anhydrase-II (CA-II) inhibition and structure–activity relationship studies of cinnamaldehyde-clubbed thiosemicarbazones derivatives. The derivatives showed potent activities in the range of 10.3 ± 0.62–46.6 ± 0.62 µM. Among all the synthesized derivatives, compound 3n (IC50 = 10.3 ± 0.62 µM), 3g (IC50 = 12.1 ± 1.01 µM), and 3h (IC50 = 13.4 ± 0.52 µM) showed higher inhibitory activity as compared to the standard inhibitor, acetazolamide. Furthermore, molecular docking of all the active compounds was carried out to predict their behavior of molecular binding. The docking results indicate that the most active hit (3n) specifically mediate ionic interaction with the Zn ion in the active site of CA-II. Furthermore, the The199 and Thr200 support the binding of thiosemicarbazide moiety of 3n, while Gln 92 supports the interactions of all the compounds by hydrogen bonding. In addition to Gln92, few other residues including Asn62, Asn67, The199, and Thr200 play important role in the stabilization of these molecules in the active site by specifically providing H-bonds to the thiosemicarbazide moiety of compounds. The docking score of active hits are found in range of − 6.75 to − 4.42 kcal/mol, which indicates that the computational prediction correlates well with the in vitro results.

Abstract The present study reports a hydrogel-based sunlight-assisted synthesis of gold nanoparticles (Au NPs) with enhanced antimicrobial and wound healing potential. The hydrogel extracted from the seeds of Cydonia oblonga was used as a reducing and capping agent to synthesize Au NPs for the first time. The as-synthesized Au NPs were characterized for an average size, shape, surface functionalization, antimicrobial, and wound healing capabilities. The cubic and rectangular-shaped Au NPs with an average edge length of 74 ± 4.57 nm depicted a characteristic surface plasmon resonance band at 560 nm. The hydrogel-based Au NPs inhibited the growth of microorganisms in zones with 12 mm diameter. In-vitro experiments showed that a minimum inhibitory concentration of Au NPs (16 µg/mL) was sufficient to mimic the 95% growth of pathogenic microorganisms in 24 h. In vivo treatment of wounds with Au NPs in murine models revealed a 99% wound closure within 5 days. Quantitative PCR analysis performed to decipher the role of Au NPs in enhanced wound healing showed an increase in the expression levels of NANOG and CD-34 proteins.

Abstract The role of aldose reductase (ALR2) in causing diabetic complications is well-studied, with overactivity of ALR2 in the hyperglycemic state leading to an accumulation of intracellular sorbitol, depletion of cytoplasmic NADPH and oxidative stress and causing a variety of different conditions including retinopathy, nephropathy, neuropathy and cardiovascular disorders. While previous efforts have sought to develop inhibitors of this enzyme in order to combat diabetic complications, non-selective inhibition of both ALR2 and the homologous enzyme aldehyde reductase (ALR1) has led to poor toxicity profiles, with no drugs targeting ALR2 currently approved for therapeutic use in the Western world. In the current study, we have synthesized a series of N-substituted thiosemicarbazones with added phenolic moieties, of which compound 3m displayed strong and selective ALR2 inhibitory activity in vitro (IC50 1.18 µM) as well as promising antioxidant activity (75.95% free radical scavenging activity). The target binding modes of 3m were studied via molecular docking studies and stable interactions with ALR2 were inferred through molecular dynamics simulations. We thus report the N-substituted thiosemicarbazones as promising drug candidates for selective inhibition of ALR2 and possible treatment of diabetic complications.

Abstract High toxicity and extensive accessibility of fluoride and cyanide ions in diverse environmental media encouraged attention for scheming well-organized probes for their detection. Keeping in mind we have designed and synthesized thiosemicarbazone-based chemosensors RB-1, RB-2 and RB-3 for the detection of fluoride and cyanide ions. The structural elucidation of the synthesized chemosensors is done by employing different analytical techniques including nuclear magnetic resonance and electronic absorption specrtoscopies. Admirable detection limit, binding constant and fast response time (2 s) to F− and CN− ions enlarged the applications of these chemosensors. Additional confirmation of the sensing ability of these chemosensors is derived from DFT and TDDFT calculations with M06/6-311G(d,p) method by performing FMO, UV–Vis, QTAIM and global reactivity parameters elucidation. Overall results point out that investigated chemosensors are suitable candidates for sensing the F− ions. These chemosensors were successfully applied to detect F− ions in a commercial toothpaste sample.

Abstract Non-fullerene based organic compounds are considered promising materials for the fabrication of modern photovoltaic materials. Non-fullerene-based organic solar cells comprise of good photochemical and thermal stability along with longer device lifetimes as compared to fullerene-based compounds. Five new non-fullerene donor molecules were designed keeping in view the excellent donor properties of 3-bis(4-(2-ethylhexyl)-thiophen-2-yl)-5,7-bis(2ethylhexyl) benzo[1,2-:4,5-c′]-dithiophene-4,8-dione thiophene-alkoxy benzene-thiophene indenedione (BDD-IN) by end-capped modifications. Photovoltaic and electronic characteristics of studied molecules were determined by employing density functional theory (DFT) and time dependent density functional theory (TD-DFT). Subsequently, obtained results were compared with the reference molecule BDD-IN. The designed molecules presented lower energy difference (ΔΕ) in the range of 2.17–2.39 eV in comparison to BDD-IN (= 2.72 eV). Moreover, insight from the frontier molecular orbital (FMO) analysis disclosed that central acceptors are responsible for the charge transformation. The designed molecules were found with higher λmax values and lower transition energies than BDD-IN molecule due to stronger end-capped acceptors. Open circuit voltage (Voc) was observed in the higher range (1.54–1.78 V) in accordance with HOMOdonor–LUMOPC61BM by designed compounds when compared with BDD-IN (1.28 V). Similarly, lower reorganization energy values were exhibited by the designed compounds in the range of λe(0.00285–0.00370 Eh) and λh(0.00847–0.00802 Eh) than BDD-IN [λe(0.00700 Eh) and λh(0.00889 Eh)]. These measurements show that the designed compounds are promising candidates for incorporation into solar cell devices, which would benefit from better hole and electron mobility.

Abstract New-generation chemosensors desire small organic molecules that are easy to synthesise and cost-effective. As a new interdisciplinary area of research, the integration of these chemosensors into keypad locks or other advanced communication protocols is becoming increasingly popular. Our lab has developed new chemosensor probes that contain 2-nitro- (1–3) and 4-fluoro-cinnamaldehyde (4–6) and applied them to the anion recognition and sensing process. Probes 1–6 are colorimetric sensors for naked-eye detection of AcO−/CN−/F−, while probes 4–6 could differentiate between F− and AcO−/CN− anions in acetonitrile. Using the density functional theory (DFT), it was found that probes 1–6 acted as effective chemosensors. By using Probe 5 as a chemosensor, we explored colorimetric recognition of multiple anions in more detail. Probe 5 was tested in combination with a combinatorial approach to demonstrate pattern-generation capability and its ability to distinguish among chemical inputs based on concentration. After pattern discrimination using principal component analysis (PCA), we examined anion selectivity using DFT computation. In our study, probe 5 demonstrates excellent performance as a chemosensor and shows promise as a future molecular-level keypad lock system.

Abstract The global need for renewable sources of energy has compelled researchers to explore new sources and improve the efficiency of the existing technologies. Solar energy is considered to be one of the best options to resolve climate and energy crises because of its long-term stability and pollution free energy production. Herein, we have synthesized a small acceptor compound (TPDR) and have utilized for rational designing of non-fullerene chromophores (TPD1–TPD6) using end-capped manipulation in A2–A1–D–A1–A2 configuration. The quantum chemical study (DFT/TD-DFT) was used to characterize the effect of end group redistribution through frontier molecular orbital (FMO), optical absorption, reorganization energy, open circuit voltage (Voc), photovoltaic properties and intermolecular charge transfer for the designed compounds. FMO data exhibited that TPD5 had the least ΔE (1.71 eV) with highest maximum absorption (λ max ) among all compounds due to the four cyano groups as the end-capped acceptor moieties. The reorganization energies of TPD1–TPD6 hinted at credible electron transportation due to the lower values of λ e than λ h . Furthermore, open circuit voltage (Voc) values showed similar amplitude for all compounds including parent chromophore, except TPD4 and TPD5 compounds. These designed compounds with unique end group acceptors have the potential to be used as novel fabrication materials for energy devices.

Abstract Highly selective and sensitive 2,7-naphthyridine based colorimetric and fluorescence “Turn Off” chemosensors (L1-L4) for detection of Ni2+ in aqueous media are reported. The receptors (L1-L4) showed a distinct color change from yellow to red by addition of Ni2+ with spectral changes in bands at 535–550 nm. The changes are reversible and pH independent. The detection limits for Ni2+ by (L1-L4) are in the range of 0.2–0.5 µM by UV–Visible data and 0.040–0.47 µM by fluorescence data, which is lower than the permissible value of Ni2+ (1.2 µM) in drinking water defined by EPA. The binding stoichiometries of L1-L4 for Ni2+ were found to be 2:1 through Job’s plot and ESI–MS analysis. Moreover the receptors can be used to quantify Ni2+ in real water samples. Formation of test strips by the dip-stick method increases the practical applicability of the Ni2+ test for “in-the-field” measurements. DFT calculations and AIM analyses supported the experimentally determined 2:1 stoichiometries of complexation. TD-DFT calculations were performed which showed slightly decreased FMO energy gaps due to ligand–metal charge transfer (LMCT).

Abstract Current research is based on biology-oriented synthesis of sulphadiazine derivatives and determination of their urease inhibitory activity. In this regard, a series of (E)-4-(benzylideneamino)-N-(pyrimidin-2-yl)benzenesulfonamide was synthesized from sulphadiazine and substituted aromatic aldehydes. The structures of synthesized compounds were ascertained by spectroscopic techniques, such as, FTIR, NMR and HRMS analysis, and in-vitro and in-silico investigation were carried out for the inhibition of urease. Ureases are harmful for humans by producing by-products of urea (ammonia and carbon dioxide). The most active compound (3l) against urease exhibited IC50 value of 2.21 ± 0.45 µM which is 10 times more potent than the standard thiourea (20.03 ± 2.06 µM). It is noteworthy that most of our synthesized compounds showed significant to excellent activities against urease enzyme and most of them substituted by halogen or hydroxy groups at ortho and para positions in their structures. Inhibition of enzyme by the synthesized analogues was in descending order as 3l > 3a > 3b > 3q > 3e > 3o > 3s > 3t > 3g > 3k > 3r > 3f > 3m > 3p > 3n > 3j > 3i > 3h. Moreover, molecular docking studies were performed to rationalize the binding interactions of the synthesized motifs with the active pocket of the urease enzyme. The synthesized sulphadiazine derivatives (3a–u) were found to be non-toxic, and presented passive gastrointestinal absorption.

A one-pot three-component protocol was designed for cascade synthesis of novel heterocyclic amino-1,8-naphthyridines. Materials synthesis is confirmed by NMR (1H and 13C) and structures are verified by computational models. The in vitro phytotoxic and urease enzyme inhibition studies with IC50 ranges from 23.76 ± 0.027 µM to 67.46 ± 3.93 indicating significant pharmacological activity of synthesized compounds. Osiris calculations results confirm the non-mutagenicity and non-irritating patterns. Molinspiration calculations values of 3.49–3.94 indicate the permeability of the derivates through membranes. Amino-1,8-naphthyridines are used for the first time in electrochemical sensing of DNA. The mechanism of interaction between DNA and amino-1,8-naphthyridine derivatives is evaluated via a constant current potentiometric method. Different electrochemical parameters such as scan rate, binding time, and effect of concentration of DNA are optimized. The strong interaction of these compounds with the human DNA under physiological conditions justified their potential applications as biosensors after further optimization.

The exploration of novel materials with excellent nonlinear optical (NLO) features is an area of frontline investigation for scientific community from technological point of view. This study reports the novel phenothiazine-based rod-shaped and T-shaped NLO molecules which are quantum chemically designed from synthesized compounds: rod-shaped (CFA and CBA) and T-shaped (CTA, CCA and CPA). Structural tailoring was performed on D-π-π-A centered CPA chromophore and the effect of various π-spacers, as well as solvents on NLO response properties is investigated. Density functional theory (DFT) along with time dependent DFT (TDDFT) calculations have been executed at B3LYP/6-311G(d,p) functional to examine entire analysis. Results showed a smaller energy gap in structurally modified compounds as compared to reference CPA. Global reactivity parameters analysis revealed smaller hardness and larger softness values in T-shaped compounds. UV–Vis analysis of investigated molecules displayed a red shift in absorption maximum value as compared to CPA. Natural bond orbital (NBO) and frontier molecular orbital (FMO) analysis revealed the stability and intra-molecular electron transferring (ICT) process in investigated molecules. ICT showed the effective charge shift from donor to acceptor via π-spacers. Overall, promising NLO response exists in gas phase and different solvents (acetonitrile, ethyl alcohol and water). Interestingly, proposed molecule CPP presented a maximum value of linear polarizability as 1518.23 a.u and first hyperpolarizability (βtot) as 755322.39 a.u in acetonitrile solvent. In short, entitled chromophores exhibited excellent NLO properties due to their lower charge transport resistance. This NLO study may open a new topic for researchers to discover novel NLO for hi-tech submissions of modern era.

Now a days, non-fullerene organic compounds are considered with keen interest for the greener energy and potential photovoltaic devices. Herein, novel acceptor chromophores (DPDVD1-DPDVD4) were designed via small acceptor DPDVR compound with A1-π-A2-π-A1 architecture using promising approach by redistribution of end-capped acceptor moieties. The effect of end-capped acceptor moieties on designed architecture for the photophysical, photovoltaic and electronic behavior was explored using quantum chemical study. Frontier molecular orbital (FMO) findings revealed that all the molecules (DPDVD1-DPDVD4) contained narrow band gaps. The central acceptor moiety (PzDP) was responsible for the transformation of charge in DPDVD1-DPDVD4. UV–Vis data disclosed that λmax values of DPDVD1-DPDVD4 compounds were existed in visible region (537.36–517.05 nm). Interestingly, DPDVD2 exhibited the reduced band gap with broader absorption spectra among all chromophores might be due to the negative inductive effect (−I) of the terminal acceptors. The open circuit voltage (Voc) analysis was performed at the interface between standard donor polymer (PTB7) and DPDVD2. The higher value (3.34 V) of Voc was observed for DPDVD2 among reference and designed compounds. Furthermore, reorganization energy findings exploited DPDVR-DPDVD4 shown lower values of λe than λh which indicated that these chromophores were the promising candidates for electron transportation mobilities. The larger charge mobilities with greater exciton dissociation in excited state for DPDVD2 were examined, subsequently this compound showed minimum value of λe (0.015739 eV) among all chromophores. Detailed studies reveal that the entitled molecules can behave as efficient electron acceptor molecules in organic solar cells (OSCs) that make them interesting candidates for the development of inexpensive optoelectronic devices.

Using biomolecule-rich plant extracts, the conversion of metal ions to metal oxide nanoparticles via abiogenic approach is highly intriguing, environmentally friendly, and quick. The inherent inclination of plant extracts function as capping agents in the insitu synthesis. In this study, biogenic zinc oxide nanoparticles (ZnO−NPs) were synthesized using an aqueous leaf extract from Moringaoleifera. The ZnO−NPs were then mixed with carboxylated carbon nanotubes (CNTs) to create a carboxylated CNTs/biogenic ZnO composite using asol–gel method. The CNTs/ZnO composite displayed 18 mm, 16 mm, and 17 mm zones of inhibition (ZOI) against Bacillus cereus, Pseudomonas aeruginosa, and Escherichia coli, respectively. In contrast with ZnO−NPs, the produced carboxylated CNTs/ZnO composite demonstrated a 13 percent elevation in ZOI as antibacterial activity against Bacillus cereus ATCC 19659, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853. The characterization of ZnO−NPs and the carboxylated CNTs/ZnO composite were performed via FTIR, UV/Vis spectroscopy, SEM, and XRD. The XRD pattern depicted a nano−sized crystalline structure (Wurtzite) of ZnO−NPs and a carboxylated CNTs/ZnO composite. The current work comprehends a valuable green technique for killing pathogenic bacteria, and gives fresh insights into the manufacture of metal oxide composites for future research.

Tribulus terrestris L. belongs to the family Zygophyllaceae and integral part of various ancient medicinal systems including Chinese, Indian, and European to combat various health ailments. The aim of the present study was to assess the phytochemical constituents, in vitro antioxidant activity using DPPH, FRAP, and H2O2 assays, in vitro anticancer activity using MTT assay, and in vitro and in vivo anti-inflammatory properties of T. terrestris. The acute and sub-acute toxicity of extracts exhibiting most biological potential was examined using murine models. Liquid–liquid partitioning followed by RP–HPLC sub-fraction of crude extract was performed. After that, ESI-MS/MS analysis was done for the timid identification of bioactive metabolites responsible for bioactivities of sub-fractions and HPLC analysis to quantify the compounds using external standards. Among all extracts, T. terrestris methanol extract was noted to hold maximum phenolic (341.3 mg GAE/g) and flavonoid (209 mg QE/g) contents, antioxidant activity in DPPH (IC50 71.4 µg/mL), FRAP (35.3 mmol/g), and H2O2 (65.3% inhibition) assays, anti-inflammatory activities in vitro at 400 µg/mL (heat-induced hemolysis, % inhibition 68.5; egg albumin denaturation, % inhibition 75.6%; serum albumin denaturation, % inhibition 80.2), and in vivo at 200 mg/kg (carrageenan-induced paw edema, % inhibition 69.3%; formaldehyde-induced paw edema, % inhibition 71.3%) and anticancer activity against breast cancer cell (MCF-7) proliferation (IC50 74.1 µg/mL). Acute and sub-acute toxicity studies recorded with no change in body weight, behavior, hematological, serum, and histopathological parameters in treated rats with T. terrestris methanol extracts when compared to control group. Fraction B obtained through liquid–liquid partitioning resulted in more bioactive potential as compared to the parent methanol extract. RP–HPLC analysis of fraction B resulted with four sub-fractions (TBTMF1-TBTMF4), wherein TBTMF3 delineated notable bioactive capabilities as compared to other fractions and parent methanol extract. ESI-MS/MS analysis of TBTMF3 resulted with tentative identification of myricetin, rutin, liquitrigenin, physcion, and protodioscin. It can be stated that T. terrestris is a potential bearing herb and findings of current study further verify the claims made in ancient medicinal systems. However, after investigation of each identified compound, it must be considered for drug discovery.

Carbonic anhydrase-II (CA-II) is associated with glaucoma, malignant brain tumors, and renal, gastric, and pancreatic carcinomas and is mainly involved in the regulation of the bicarbonate concentration in the eyes. CA-II inhibitors can be used to reduce the intraocular pressure usually associated with glaucoma. In search of potent CA-II inhibitors, a series of quinazolinones derivatives (4a-p) were synthesized and characterized by IR and NMR spectroscopy. The inhibitory potential of all the compounds was evaluated against bovine carbonic anhydrase-II (bCA-II) and human carbonic anhydrase-II (hCA-II), and compounds displayed moderate to significant inhibition with IC50 values of 8.9–67.3 and 14.0–59.6 μM, respectively. A preliminary structure-activity relationship suggested that the presence of a nitro group on the phenyl ring at R position contributes significantly to the overall activity. Kinetics studies of the most active inhibitor, 4d, against both bCA-II and hCA-II were performed to investigate the mode of inhibition and to determine the inhibition constants (Ki). According to the kinetics results, 4d is a competitive inhibitor of bCA-II and hCA-II with Ki values of 13.0 ± 0.013 and 14.25 ± 0.017 μM, respectively. However, the selectivity index reflects that the compounds 4g and 4o are more selective for hCA-II. The binding mode of these compounds within the active sites of bCA-II and hCA-II was investigated by structure-based molecular docking. The docking results are in complete agreement with the experimental findings.

Peganum harmala (P. harmala) belongs to the family Zygophyllaceae, and is utilized in the traditional medicinal systems of Pakistan, China, Morocco, Algeria, and Spain to treat several chronic health disorders. The aim of the present study was to identify the chemical constituents and to evaluate the antioxidant, anti-inflammatory, and toxicity effects of P. harmala extracts both in vitro and in vivo. Sequential crude extracts including 100% dichloromethane, 100% methanol, and 70% aqueous methanol were obtained and their antioxidant and anti-inflammatory effects evaluated both in vitro and in vivo. The anti-inflammatory effect of the extract was investigated using the carrageenan-induced paw edema method in mice, whereas the toxicity of the most active extract was evaluated using an acute and subacute toxicity rat model. In addition, we have used the bioassay-guided approach to obtain potent fractions, using solvent–solvent partitioning and reversed phase high performance liquid chromatography from active crude extracts; identification and quantification of compounds from the active fractions was achieved using electrospray ionization mass spectrometry and high performance liquid chromatography techniques. Results revealed that the 100% methanol extract of P. harmala exhibits significant in vitro antioxidant activity in DPPH assay with an IC50 of 49 µg/mL as compared to the standard quercetin with an IC50 of 25.4 µg/mL. The same extract exhibited 63.0% inhibition against serum albumin denaturation as compared to 97% inhibition by the standard diclofenac sodium in an in vitro anti-inflammatory assay, and in vivo anti-inflammatory against carrageenan-induced paw edema (75.14% inhibition) as compared to 86.1% inhibition caused by the standard indomethacin. Furthermore, this extract was not toxic during a 14 day trial of acute toxicity when given at a dose of 3 g/kg, indicating that the lethal dose (LD50) of P. harmala methanol extract was greater than 3 g/kg. P. harmala methanolic fraction 2 obtained using bioassay-guided fractionation showed the presence of quinic acid, peganine, harmol, harmaline, and harmine, confirmed by electrospray ionization mass spectrometry and quantified using external standards on high performance liquid chromatography. Taken all together, the current investigation further confirms the antioxidant, anti-inflammatory, and safety aspects of P. harmala, which justifies its use in folk medicine.

New thiosemicarbazide-linked acridines 3a–c were prepared and investigated as chemosensors for the detection of biologically and environmentally important anions. The compounds 3a–c were found selective for fluoride (F−) with no affinity for other anions, i.e. −OAc, Br−, I−, HSO4−, SO42−, PO43−, ClO3−, ClO4−, CN− and SCN−. Further, upon the gradual addition of a fluoride anion (F−) source (tetrabutylammonium fluoride), a well-defined change in colour of the solution of probes 3a–c was observed. The anion-sensing process was studied in detail via UV–visible absorption, fluorescence and 1H-NMR experiments. Moreover, during the synthesis of acridine probes 3a–c nickel fluoride (NiF2), a rarely explored transition metal fluoride salt, was used as the catalyst. Theoretical studies via density functional theory were also carried out to further investigate the sensing and anion (F−) selectivity pattern of these probes.

The title compound, C24H14O9·H2O, displays a cup-shaped form. The water molecule is disordered over two set of sites with an occupancy ratio of 0.78:0.22. The molecule of the compound has four stereocenters and corresponds to the SSRR/RRSS diastereoisomer. In the molecule, the maximum dihedral angle between the planar benzene rings is 80.40 (4)°. The H atoms of the hydroxy groups are engaged in hydrogen bonding, forming infinite chains parallel to the a axis. These chains are interlinked through water molecules, resulting in the formation of a two-dimensional network parallel to the (001) plane. Futhermore C—H...O, C—H...π and slipped π–π interactions result in the formation of a three-dimensional network.

The name of one of the authors in the paper by Hussain et al. [Acta Cryst. (2010), E66, o1881] is corrected.

In the title compound, C14H16N2O3S, the dihedral angle between the phenyl and 5-methylfuran groups is 54.89 (14)° and the C=N bond assumes a trans conformation. In the crystal, inversion dimers linked by pairs of N—H...O hydrogen bonds generate R22(8) ring motifs. The dimers are interlinked by N—H...N hydrogen bonds, resulting in the formation of infinite chains extending along the b axis. The packing is consolidated by weak C—H...π interactions.

In the title compound, C15H13NO4·H2O, the organic molecule adopts a V-shaped conformation in which the dihedral angle between the five-membered rings is 68.33 (5)°. The cyclohexenone ring adopts an envelope conformation, with one of the methylene C atoms displaced by 0.607 (4) Å from the plane through the other atoms. In the crystal, intermolecular N—H...(O,O) and O—H...O hydrogen bonds link the components into (001) sheeets and C–H...O interactions and aromatic π–π stacking [centroid–centroid separation = 3.6176 (19) Å] help to consolidate the packing.

In the title compound, C14H12ClN3O2·H2O, the benzene ring and the pyridine rings are oriented at a dihedral angle of 57.73 (12)° and an intramolecular O—H...N hydrogen bond generates an S(6) ring. In the crystal, the water molecule forms O—H...O and O—H...N hydrogen bonds to the organic molecule, leading to chains containing R44(16) loops. In addition, weak aromatic π–π stacking interactions between the centroids of pyridine rings [at distance of 3.864 (2) and 4.013 (2) Å] and C—H...π interactions occur.

The asymmetric unit of title compound, C17H14N2O3, contains three independent molecules. In one of these molecules, the 5-methyl-2-furyl group is disordered over two sets of sites with an occupancy ratio of 0.747 (3):0.253 (3). In the two ordered molecules, the furan and naphthalene rings are oriented at dihedral angles of 11.05 (12) and 32.2 (5)°. In the disordered molecule, the furan rings with major and minor occupancies are oriented at dihedral angles of 41.4 (2) and 26.6 (13)°, respectively, with the corresponding naphthalene ring. An intramolecular O—H...O hydrogen bond occurs within each molecule. In the crystal, molecules are linked by N—H...O, N—H...(N,O) and C—H...O interactions.

In the title compound, C15H14N2O3, the phenyl ring is disordered over two set of sites with an occupancy ratio of 0.810 (3):0.190 (3); the dihedral angle between the two components is 72.3 (4)°. The benzene and phenyl rings are oriented at dihedral angles of 69.18 (8) and 26.0 (5)° (major and minor orientations, respectively), and an intramolecular O—H...O hydrogen bond occurs. In the crystal, molecules are linked by N—H...O, O—H...O and C—H...O interactions, generating a three-dimensional network.

In the title compound, C9H9FN2O, the dihedral angle between the fluorobenzene ring and the mean plane of the side chain is 15.59 (14)°. In the crystal, the molecules form inversion dimers linked by pairs of N—H...O hydrogen bonds, resulting in R22(8) loops. These dimers are reinforced by C—H...O interactions.

The structure of the title compound, C9H9ClN2O, consists of centrosymmetric dimers due to intermolecular N—H...O hydrogen bonding, forming R22(8) ring motifs. The dihedral angle between the p-chlorophenyl unit and the remaining heavy-atom group is 6.77 (17)°.

In title compound, C11H8BrN3OS, the dihedral angle between the two aromatic rings is 27.61 (14)° and the Br atom is disordered over two sites with an occupancy ratio of 0.804 (2):0.196 (2). In the crystal, the molecules are linked by N—H...O, C—H...O and C—H...N interactions, resulting in chains.

The title compound, C7H8N2O2, is almost planar (r.m.s. deviation for non-H atoms = 0.029 Å). In the crystal, inversion dimers linked by pairs of N—H...O hydrogen bonds generate an R22(8) ring motif.

In the title compound, C18H17N3O4, the furyl and phenyl rings are inclined at almost right angles [85.77 (7) and 63.25 (7)°, respectively] to the central imidazo[1,2-a]pyridinyl unit. The structure displays both inter- and intramolecular N—H...O hydrogen bonding.

In the title compound, C19H18FN3O4, the fused pyridine and pyrimidine rings adopt half-chair conformations. The structure displays intramolecular N—H...O and intermolecular N—H...F hydrogen bonding.