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Cancers account for many deaths worldwide and natural compounds and their derivatives are interesting chemotherapeutic agents for cancer drug development. In this study, a natural compound 3,3’4-trimethoxy-4’-rutinosylellagic acid (TR2) and its acetylated derivative 3,3’4-trimethoxy-4’-hexaacetylrutinosylellagic acid (TR22) were evaluated for their antioxidant and anticancer effects against estrogen sensitive (MCF-7) and estrogen non-sensitive (MDA-MB 231) breast adenocarcinoma. In the β-Carotene-linoleic acid assay, DPPH• radical scavenging and CUPRAC assay, the compound TR2 had better activity than the standard α-Tocopherol, while in the ABTS•+ assay, it was more active than both standards α- α-Tocopherol and BHA. Both compounds had good antioxidant effects with TR2 being more active than TR22. Both compounds inhibited growth of breast carcinoma cells when compared to the untreated controls after 72 h. Compound TR22 significantly (p < 0.001) inhibited proliferation of both MCF-7 and MDA-MB 231 breast carcinoma cell lines suggesting that acetylation reaction improves inhibition of breast cancer cells growth. On the contrary, TR2 exhibited better inhibitory effect of clone formation than TR22 suggesting that acetylation reduces the activity in this assay. Both compounds inhibited migration of the cancer cells when compared to the untreated control cells and compound TR2 exhibited greater cellular anti-migration effect than TR22 at the same concentration and after the same period of incubation. Molecular docking studies supplemented the results and revealed that TR2 and TR22 had appreciable interactions with tyrosine kinase with negative binding energies suggesting that they are potent receptor tyrosine kinase inhibitors which can impede on cancer progression.

ABSTRACTThe Juglans regia root aqueous extract (JRRAE) phytochemical variability and the investigation of their antimicrobial, antibiofilm, insecticidal, and anti-leishmanial properties were studied. As a result, the JRRAE chemical profile revealed the presence of biomolecules using UV, HPLC, and FT-IR analysis. The investigations showed marked antibacterial activities, highlighted inhibited biofilm formation, induced lethality Leishmania amazonensis promastigotes (50%), and possess an insecticidal activity at 100 µg/ml. A molecular docking study was performed against S. aureus gyrase, S. aureus tyrosyl-tRNA synthetase, human peroxiredoxin 5, cyclooxygenase-2, and trypanothione reductase and confirmed that the activities are mainly due to coumarin, epicatechin, juglone, epicatechin, and epicatechin presence, respectively. The stability of these complexes is essentially related to the strong hydrogen bonds formed between the most active compounds and the binding site amino acids. The identified compounds were found to pass the absorption, distribution, metabolism, and excretion property as well as five Lipinski’s rules with good drug-likeness and pharmacokinetic behavior.

Alzheimer’s disease (AD) and diabetes are non-communicable diseases with global impacts. Inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are suitable therapies for AD, while α-amylase and α-glucosidase inhibitors are employed as antidiabetic agents. Compounds were isolated from the medicinal plant Terminalia macroptera and evaluated for their AChE, BChE, α-amylase, and α-glucosidase inhibitions. From 1H and 13C NMR data, the compounds were identified as 3,3′-di-O-methyl ellagic acid (1), 3,3′,4′-tri-O-methyl ellagic acid-4-O-β-D-xylopyranoside (2), 3,3′,4′-tri-O-methyl ellagic acid-4-O-β-D-glucopyranoside (3), 3,3′-di-O-methyl ellagic acid-4-O-β-D-glucopyranoside (4), myricetin-3-O-rhamnoside (5), shikimic acid (6), arjungenin (7), terminolic acid (8), 24-deoxysericoside (9), arjunglucoside I (10), and chebuloside II (11). The derivatives of ellagic acid (1–4) showed moderate to good inhibition of cholinesterases, with the most potent being 3,3′-di-O-methyl ellagic acid, with IC50 values of 46.77 ± 0.90 µg/mL and 50.48 ± 1.10 µg/mL against AChE and BChE, respectively. The compounds exhibited potential inhibition of α-amylase and α-glucosidase, especially the phenolic compounds (1–5). Myricetin-3-O-rhamnoside had the highest α-amylase inhibition with an IC50 value of 65.17 ± 0.43 µg/mL compared to acarbose with an IC50 value of 32.25 ± 0.36 µg/mL. Two compounds, 3,3′-di-O-methyl ellagic acid (IC50 = 74.18 ± 0.29 µg/mL) and myricetin-3-O-rhamnoside (IC50 = 69.02 ± 0.65 µg/mL), were more active than the standard acarbose (IC50 = 87.70 ± 0.68 µg/mL) in the α-glucosidase assay. For α-glucosidase and α-amylase, the molecular docking results for 1–11 reveal that these compounds may fit well into the binding sites of the target enzymes, establishing stable complexes with negative binding energies in the range of −4.03 to −10.20 kcalmol−1. Though not all the compounds showed binding affinities with cholinesterases, some had negative binding energies, indicating that the inhibition was thermodynamically favorable.

A retro-Claisen reaction of 1-(4-oxo-4H-pyrido [1,2-a]pyrimidin-3-yl)butane-1,3-dione, 3, in the presence of potassium hydroxide and 4-dimethylamino-pyridine has been carried out, leading to 4-(dimethylamino)pyridin-1-ium 2-methyl-4-oxo-pyrido [1,2-a]pyrimidine-3-carboxylate 5. A plausible mechanism explaining the formation of the title compound has been proposed. A single-crystal X-ray diffraction analysis confirms the crystal structure of the isolated organic salt (5). In the crystal, the title compound adopts a layered structure where there are stacks of cations and anions formed by slipped π-stacking interactions. These stacks are linked by regions consisting of water molecules that are hydrogen-bonded together. DFT and Hirshfeld surface analysis supported the experimental results of the molecular geometry and the intercontacts between different units in the crystal. The druglikeness, ADMET properties, and predicted targets were investigated, and the observed results suggest that 5 may act as a carbonic anhydrase I inhibitor. The assumption is confirmed by docking 5 into the active binding site of carbonic anhydrase, which shows it to have good binding affinities and to form stable complexes with the active residues of carbonic anhydrase I.

An efficient pathway was disclosed for the synthesis of 3-chloro-6-nitro-1H-indazole derivatives by 1,3-dipolar cycloaddition on dipolarophile compounds 2 and 3. Faced the problem of separation of two regioisomers, a click chemistry method has allowed us to obtain regioisomers of triazole-1,4 with good yields from 82 to 90% were employed. Also, the antileishmanial biological potency of the compounds was achieved using an MTT assay that reported compound 13 as a promising growth inhibitor of Leishmania major. Molecular docking demonstrated highly stable binding with the Leishmania trypanothione reductase enzyme and produced a network of hydrophobic and hydrophilic interactions. Molecular dynamics simulations were performed for TryR-13 complex to understand its structural and intermolecular affinity stability in a biological environment. The studied complex remained in good equilibrium with a structure deviation of ∼1–3 Å. MM/GBSA binding free energies illustrated the high stability of TryR-13 complex. The studied compounds are promising leads for structural optimisation to enhance the antileishmanial activity.

Three different simple and polymeric hydrazide derivatives have been synthesized, evaluated and investigated as corrosion inhibitors for mild steel in 1 M hydrochloric acid medium. The corrosion inhibition performance of these additives was evaluated using electrochemical impedance spectroscopy (EIS) and polarizations measurements. The inhibition efficiency obtained from polarization measurement followed the order of PACAH > ACAH > CAH. The inhibition efficiency of the polyhydrazide derivative (PACAH) at concentration of 50 and 500 ppm was found to be 90.66 and 96.79% respectively, while 500 ppm of cyanoacetohydrazide (CAH) was 39.79% and for the monomer N-acryloyl-N′-cyanoacetohydrazide (ACAH) was 88.66%.The surface morphology of the steel electrode was studied with and without the inhibitor after immersion in 1 M HCl solution for 6 h using SEM, EDAX and AFM measurements. The results showed an improvement in the surface morphology where the flawed regions were repaired and the cracks were healed. This improvement was attributed to the adsorption of the inhibitor molecules and the formation of a protective layer at the steel surface. The adsorption isotherm indicated a spontaneous physical adsorption of the inhibitor on the surface of mild steel electrode. Quantum chemical calculation was used to correlate the inhibition efficiencies data of the hydrazide derivatives with their electronic structural parameters. Theoretical calculations supported and elucidated the experimental results.

Graptophyllum pictum is a tropical plant noticeable for its variegated leaves and exploited for various medicinal purposes. In this study, seven compounds, including three furanolabdane diterpenoids, i.e., Hypopurin E, Hypopurin A and Hypopurin B, as well as with Lupeol, β-sitosterol 3-O-β-d-glucopyranoside, stigmasterol 3-O-β-d-glucopyranoside and a mixture of β-sitosterol and stigmasterol, were isolated from G. pictum, and their structures were deduced from ESI-TOF-MS, HR-ESI-TOF-MS, 1D and 2D NMR experiments. The compounds were evaluated for their anticholinesterase activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BchE), as well as their antidiabetic potential through inhibition of α-glucosidase and α-amylase. For AChE inhibition, no sample had IC50 within tested concentrations, though the most potent was Hypopurin A, which had a percentage inhibition of 40.18 ± 0.75%, compared to 85.91 ± 0.58% for galantamine, at 100 µg/mL. BChE was more susceptible to the leaves extract (IC50 = 58.21 ± 0.65 µg/mL), stem extract (IC50 = 67.05 ± 0.82 µg/mL), Hypopurin A (IC50 = 58.00 ± 0.90 µg/mL), Hypopurin B (IC50 = 67.05 ± 0.92 µg/mL) and Hypopurin E (IC50 = 86.90 ± 0.76 µg/mL). In the antidiabetic assay, the furanolabdane diterpenoids, lupeol and the extracts had moderate to good activities. Against α-glucosidase, lupeol, Hypopurin E, Hypopurin A and Hypopurin B had appreciable activities but the leaves (IC50 = 48.90 ± 0.17 µg/mL) and stem (IC50 = 45.61 ± 0.56 µg/mL) extracts were more active than the pure compounds. In the α-amylase assay, stem extract (IC50 = 64.47 ± 0.78 µg/mL), Hypopurin A (IC50 = 60.68 ± 0.55 µg/mL) and Hypopurin B (IC50 = 69.51 ± 1.30 µg/mL) had moderate activities compared to the standard acarbose (IC50 = 32.25 ± 0.36 µg/mL). Molecular docking was performed to determine the binding modes and free binding energies of Hypopurin E, Hypopurin A and Hypopurin B in relation to the enzymes and decipher the structure–activity relationship. The results indicated that G. pictum and its compounds could, in general, be used in the development of therapies for Alzheimer’s disease and diabetes.

In this work, we describe the synthesis of new macrocycles derived from 3-phenyl-1,2,4-triazole-5-thione 1 in a heterogeneous medium using liquid–solid phase transfer catalysis (PTC) conditions. The structures of the two compounds (3 and 4) isolated were elucidated based on spectral data (1H-NMR, 13C-NMR) and confirmed in the case of 3-phenyl-1,2,4-triazolo [3,4-h]-13,4--thiaza-11-crown-4 (3) by a single-crystal X-ray diffraction analysis. Furthermore, the experimental spectral and the X-ray geometrical parameters were compared with their corresponding predicted ones obtained at the B3LYP/6-311++G(d,p) level of theory. The intercontacts between crystal units were investigated through Hirshfeld surface analysis. The drug-like macrocycles were predicted using ADMET and drug-likeness properties, which showed that 3 may act as an inhibitor of DNA-dependent protein kinase (DNA-PK). This assumption was confirmed by the well-binding fitting of 3 into the binding site of DNA-PK and the formation of a stable 3-DNA-PK complex with a binding energy of −7 kcal-mol−1. Finally, the anticancer activity of 3 was assessed by an MTT assay against A549 cells, which showed that 3 has moderate anticancer activity compared to that of the doxorubicin reference drug.

Andrographolide, the major constituent from the terrestrial plant Andrographis paniculata is a much-studied bioactive ent-labdane diterpene lactone and has become an important medicinal intermediate. Its structure as determined by X-ray crystallography has been applied in molecular docking studies to explain biological activities. Nevertheless, recently there has been a number of conflicting reports concerning the stereochemistry at the C-14 and C-10 positions affecting the absolute configuration (AC) of the compound. Since a lack of information on the molecular flexibility of the molecule can lead to misleading conclusions on biological activity, a conformational analysis of the molecule in the solution state was necessary. The conformational analysis was performed by the Spartan14 package using the Merck Molecular Force Field (MMFF). The exciton chirality method in electronic circular dichroism spectroscopy (ECM-ECD) and vibrational circular dichroism (VCD) techniques were then jointly employed to re-establish the AC of andrographolide. Theoretical calculations were performed using TD-DFT methods by using the hybrid functionals B3LYP and CAM-B3LYP combined with 6-31G(d,p) basis set. Long-range exciton coupling of 2-naphthoyl chromophores at C-14 and C-19 led to the establishment of the AC to be 3R, 4R, 5S, 9R, 10R and 14S. Comparison between the theoretical VCD data of 14-S and 14-R stereoisomer confirmed a configuration of S at C-14 position instead of R.

Poly(salicylic acid) PSA has been electrochemically deposited onto a Pt electrode. The kinetics of the polymerization reaction has been studied. The polymer structure was confirmed and characterized using IR spectroscopy, XRD, SEM, and TGA analysis. The deposited PSA was then collected from the Pt surface and tested as a corrosion inhibitor for a mild steel electrode in an aqueous medium of 1 M sulfuric acid. The corrosion behavior was then evaluated using potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). Corrosion measurements showed that the inhibition efficiency of 20, 50, and 100 ppm of PSA was 33, 57, and 74%, respectively. The inhibition mechanism was proved using adsorption isotherms as well as quantum calculations. The inhibition of the corrosion process was due to the adsorption of PSA on the steel surface, which was found to comply with the Langmuir adsorption isotherm.

An enhanced acetylcholinesterase (AChE) activity is a hallmark in early stages of Alzheimer's ailment that results in decreased acetylcholine (ACh) levels, which in turn leads to cholinergic dysfunction and neurodegeneration. Consequently, inhibition of both AChE and butyrylcholinesterase (BChE) is important to prolong ACh activity in synapses for the enhanced cholinergic neurotransmission. In this study, a series of new fluoroquinolone derivatives (7a-m) have synthesized and evaluated for AChE and BChE inhibitory activities. The screening results suggested that 7 g bearing ortho fluorophenyl was the most active inhibitor against both AChE and BChE, exhibiting IC50 values of 0.70 ± 0.10 µM and 2.20 ± 0.10 µM, respectively. The structure–activity relationship (SAR) revealed that compounds containing electronegative functions (F, Cl, OMe, N and O) at the ortho position of the phenyl group exhibited higher activities as compared to their meta- and/or para substituted counterparts. Molecular docking studies of synthesized compounds 7a, 7g, 7j and 7l docked into the active site of AChE and 7a-f docked into the active site of BChE revealed that these compounds exhibited conventional H-bonding along with π-π interaction with the active residues of AChE through their electronegative functions and phenyl ring, respectively. All the synthesized compounds are characterized by spectroscopic methods including FT-IR, 1H- and 13C NMR as well as elemental analysis. This is the first example of fluoroquinolone-based cholinesterase inhibitors.

Alzheimer is a prolonged neurodegenerative disease which degenerate the brain cells and particularly affects the person ability to function independently. Despite of dynamic research, there is no proper treatment but can limit their persistent effect in early stages. In search of more potent drug for Alzheimer treatment, we have synthesized indole-based sulfonamide derivatives (1–17). All analogs were screened to find out lead candidate against acetylcholinesterase enzyme under positive control of donepezil as standard drug. Herein this study, analogs 1–4, 6–9, and 13–15 showed potent inhibition while kinetic studies further confirmed their mode of inhibition. All the synthesized analogs were characterized through HR-EI-MS, 1H NMR and 13C NMR spectroscopic techniques.

In the title quinoline derivative, C14H14ClNO3, there is an intramolecular C—H...O hydrogen bond forming an S(6) graph-set motif. The molecule is essentially planar with the mean plane of the ethyl acetate group making a dihedral angle of 5.02 (3)° with the ethyl 6-chloro-2-ethoxyquinoline mean plane. In the crystal, offset π–π interactions with a centroid-to-centroid distance of 3.4731 (14) Å link inversion-related molecules into columns along the c-axis direction. Hirshfeld surface analysis indicates that H...H contacts make the largest contribution (50.8%) to the Hirshfeld surface.

Abstract Background Indole based thiadiazole derivatives (1–22) have synthesized, characterized by NMR and HREI-MS and evaluated for β-Glucuronidase inhibition. All compounds showed outstanding β-glucuronidase activity with IC50 values ranging between 0.5 ± 0.08 to 38.9 ± 0.8 µM when compared with standard d-saccharic acid 1,4 lactone (IC50 value of 48.1 ± 1.2 µM). The compound 6, a 2,3-dihydroxy analog was found the most potent among the series with IC50 value 0.5 ± 0.08 µM. Structure activity relationship has been established for all compounds. To confirm the binding interactions of these newly synthesized compounds, molecular docking study have been carried out which reveal that these compounds established stronger hydrogen bonding networks with active site residues.

This paper reports the synthesis, characterization, anticancer screening and quantum chemical calculation of a tetradentate Schiff base 2,2'-((1E,1'E)-((2,2-dimethylpropane-1,3-diyl)bis- (azanylylidene))bis(methanylylidene))bis(4-fluorophenol) (L2F) and its Pd (II) complex (PdL2F). The compounds were characterized via UV-Visible, NMR, IR spectroscopy and single crystal x-ray diffraction. Density Functional Theory (DFT) and time-dependent DFT calculations in gas and solvent phases were carried out using B3LYP, B3P86, CAM-B3LYP and PBE0 hybrid functionals combined with LanL2DZ basis set. Complexation of L2F to form PdL2F was observed to cause a bathochromic shift of the maximum absorption bands of n-π* from 327 to 410 nm; an upfield shift for δ (HC = N) from 8.30 to 7.96 ppm and a decreased wavenumber for ν(C = N) from 1637 to 1616 cm-1. Overall, the UV-Vis, NMR and IR spectral data are relatively well reproduced through DFT and TD-DFT methods. L2F and PdL2F showed IC50 of 90.00 and 4.10 μg/mL, respectively, against human colorectal carcinoma (HCT116) cell lines, signifying increased anticancer activity upon complexation with Pd (II).

This paper reports the synthesis, characterisation and DFT analysis of an N,O bidentate Schiff base, ((E)-(4-methoxybenzylimino)methyl)phenol, (L1c) and its Ni(II) and Pd(II) complexes. The structures were elucidated via elemental analysis, UV–Visible, NMR, IR and single crystal X-ray diffraction. Complexation of L1c with Ni(II) and Pd(II) was observed to induce different degrees of bathochromic effect on n → π∗ and π → π∗ electronic transitions. A comparison of the experimental data of UV–Visible, NMR, IR and X-ray with those calculated using DFT and TD-DFT methods where five hybrid functionals were tested in gas, IEF-PCM and SS-PCM models was also carried out. The results show that the reproduction of maximum absorption bands n → π∗ and π → π∗ is strongly related to the tested hybrid functionals and solvatochromic effects. Relatively good concordance was obtained between experimental and calculated NMR chemical shifts, IR and X-ray parameters. A bioactivity evaluation against HCT116 and Escherichia coli displayed that the parent ligand L1c is a more superior anticancer and antibacterial agent than the positive controls of 5FU and gentamicin respectively. However, both complexes showed poor activity as anticancer agent and no activity observed against tested bacteria.

Previously, we synthesized triazoloquinazolines 1-14 and characterized their structure. In this study, we aimed to evaluate the in vitro activity of the targets 1-14 as α-glucosidase inhibitors using α-glucosidase enzyme from Saccharomyces cerevisiae type 1. Among the tested compounds, triazoloquinazolines 14, 8, 4, 5, and 3 showed the highest inhibitory activity (IC50 = 12.70 ± 1.87, 28.54 ± 1.22, 45.65 ± 4.28, 72.28 ± 4.67, and 83.87 ± 5.12 μM, respectively) in relation to that of acarbose (IC50 = 143.54 ± 2.08 μM) as a reference drug. Triazoloquinazolines were identified herein as a new class of potent α-glucosidase inhibitors. Molecular docking results envisaged the plausible binding interaction between the target triazoloquinazolines and α-glucosidase enzyme and indicated considerable interaction with the active site residues.

In this study, we investigate the phytochemical profile, anticancer, and antioxidant activities of Teucrium polium methanolic extract using both in vitro and in silico approaches. The results showed the identification of 29 phytochemical compounds belonging to 13 classes of compounds and 20 tripeptides using High Resolution-Liquid Chromatography Mass Spectrometry (HR-LCMS). 13R-hydroxy-9E,11Z octadecadienoic acid, dihydrosamidin, valtratum, and cepharantine were the main compounds identified. The tested extract showed promising antioxidant activities (ABTS-IC50 = 0.042 mg/mL; 1,1-diphenyl-2-picrylhydrazyl (DPPH)-IC50 = 0.087 mg/mL, β-carotene-IC50 = 0.101 mg/mL and FRAP-IC50 = 0.292 mg/mL). Using both malignant Walker 256/B and MatLyLu cell lines, T. polium methanolic extract showed a dose/time-dependent antitumor activity. The molecular docking approach revealed that most of the identified molecules were specifically binding with human peroxiredoxin 5, human androgen, and human progesterone receptors with high binding affinity scores. The obtained results confirmed that T. polium is a rich source of bioactive molecules with antioxidant and antitumor potential.

We synthesized 10 analogs of benzimidazole-based thiosemicarbazide 1 (a–j) and 13 benzimidazole-based Schiff bases 2 (a–m), and characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) inhibition activities. All the synthesized analogs showed varying degrees of acetylcholinesterase and butyrylcholinesterase inhibitory potentials in comparison to the standard drug (IC50 = 0.016 and 4.5 µM. Amongst these analogs 1 (a–j), compounds 1b, 1c, and 1g having IC50 values 1.30, 0.60, and 2.40 µM, respectively, showed good acetylcholinesterase inhibition when compared with the standard. These compounds also showed moderate butyrylcholinesterase inhibition having IC50 values of 2.40, 1.50, and 2.40 µM, respectively. The rest of the compounds of this series also showed moderate to weak inhibition. While amongst the second series of analogs 2 (a–m), compounds 2c, 2e, and 2h having IC50 values of 1.50, 0.60, and 0.90 µM, respectively, showed moderate acetylcholinesterase inhibition when compared to donepezil. Structure Aactivity Relation of both synthesized series has been carried out. The binding interactions between the synthesized analogs and the enzymes were identified through molecular docking simulations.

We have developed a new idea to synthesize a key intermediate molecule by utilizing deep eutectic solvent (DES) and ultrasound in a multistep reaction to ensure process cost-effectiveness. To confirm the stability of reagents with DES, electronic energies were calculated at the B3LYP/6-31+G(d,p) level of theory. DES stabilized the reagents mainly due to strong intermolecular hydrogen bonding. Key intermediate (3) and final compounds (4a−n) were synthesized in a higher yield of 95% and 80%−88%, respectively. Further, final compounds (4a−n) were assessed for their anti-inflammatory, analgesic, ulcerogenic, and lipid peroxidation. The compounds 4f, 4g, 4j, 4l, and 4m showed good anti-inflammatory activity, while 4f, 4i, and 4n exhibited very good analgesic activity as compared to the standard drug. The ulcerogenicity of selected compounds was far less than the indomethacin. The ligands had also shown a good docking score (4f = −6.859 kcal/mol and 4n = −7.077 kcal/mol) as compared to control indomethacin (−6.109 kcal/mol) against the target protein COX-2. These derivatives have the potential to block this enzyme and can be used as NSAID. The state-of-art DFT theory was used to validate the lipid peroxidation mechanism of the active compounds which was in good agreement with the variations of BDEs and IP of the tested compounds.

The organic molecule in the title hydrate, C12H13NO3S·H2O, is folded across the S...N vector. Chains two molecules thick extending along the a-axis direction are formed by N—H...O and O—H...O hydrogen bonds. These interactions are reinforced by C—H...S hydrogen bonds and offset π-stacking interactions between centrosymmetrically related benzene rings. The chains are associated through C—H...O hydrogen bonds.

A series of 21 compounds isolated from Curcuma zedoaria was subjected to cytotoxicity test against MCF7; Ca Ski; PC3 and HT-29 cancer cell lines; and a normal HUVEC cell line. To rationalize the structure–activity relationships of the isolated compounds; a set of electronic; steric and hydrophobic descriptors were calculated using density functional theory (DFT) method. Statistical analyses were carried out using simple and multiple linear regressions (SLR; MLR); principal component analysis (PCA); and hierarchical cluster analysis (HCA). SLR analyses showed that the cytotoxicity of the isolated compounds against a given cell line depend on certain descriptors; and the corresponding correlation coefficients (R2) vary from 0%–55%. MLR results revealed that the best models can be achieved with a limited number of specific descriptors applicable for compounds having a similar basic skeleton. Based on PCA; HCA and MLR analyses; active compounds were classified into subgroups; which was in agreement with the cell based cytotoxicity assay.

Curcumenol and curcumenone are two major constituents of the plants of medicinally important genus of Curcuma, and often govern the pharmacological effect of these plant extracts. These two compounds, isolated from C. zedoaria rhizomes were studied for their binding to human serum albumin (HSA) using the fluorescence quench titration method. Molecular docking was also performed to get a more detailed insight into their interaction with HSA at the binding site. Additions of these sesquiterpenes to HSA produced significant fluorescence quenching and blue shifts in the emission spectra of HSA. Analysis of the fluorescence data pointed toward moderate binding affinity between the ligands and HSA, with curcumenone showing a relatively higher binding constant (2.46 × 105 M−1) in comparison to curcumenol (1.97 × 104 M−1). Cluster analyses revealed that site I is the preferred binding site for both molecules with a minimum binding energy of −6.77 kcal·mol−1. However, binding of these two molecules to site II cannot be ruled out as the binding energies were found to be −5.72 and −5.74 kcal·mol−1 for curcumenol and curcumenone, respectively. The interactions of both ligands with HSA involved hydrophobic interactions as well as hydrogen bonding.

The anti-inflammatory drug predinisolone (1) was reduced to 20β-hydroxyprednisolone (2) by the marine endophytic fungus Penicilium lapidosum isolated from an alga. The structural elucidation of 2 was achieved by 1D- and 2D-NMR, MS, IR data. Although, 2 is a known compound previously obtained through microbial transformation, the data provided failed to prove the C20 stereochemistry. To solve this issue, DFT and TD-DFT calculations have been carried out at the B3LYP/6–31+G (d,p) level of theory in gas and solvent phase. The absolute configuration of C20 was eventually assigned by combining experimental and calculated electronic circular dichroism spectra and 3JHH chemical coupling constants.

Schiff bases of 3,4-dimethoxybenzenamine 1–25 were synthesized and evaluated for their antioxidant activity. All the synthesized compounds were characterized by various spectroscopic techniques. In addition, the characterizations of compounds 13, 15 and 16 were supported by crystal X-ray determinations and their geometrical parameters were compared with theoretical DFT calculations at the B3LYP level of theory. Furthermore, the X-ray crystal data of two non-crystalline compounds 8 and 18 were theoretically calculated and compared with the practical values of compounds 13, 15, 16 and found a good agreement. The compounds showed good DPPH scavenging activity ranging from 10.12 to 84.34 μM where compounds 1–4 and 6 showed stronger activity than the standard n-propyl gallate. For the superoxide anion radical assay, compounds 1–3 showed better activity than the standard.

Phenolic Schiff bases are known as powerful antioxidants. To select the electronic, 2D and 3D descriptors responsible for the free radical scavenging ability of a series of 30 phenolic Schiff bases, a set of molecular descriptors were calculated by using B3P86 (Becke’s three parameter hybrid functional with Perdew 86 correlation functional) combined with 6-31 + G(d,p) basis set (i.e., at the B3P86/6-31 + G(d,p) level of theory). The chemometric methods, simple and multiple linear regressions (SLR and MLR), principal component analysis (PCA) and hierarchical cluster analysis (HCA) were employed to reduce the dimensionality and to investigate the relationship between the calculated descriptors and the antioxidant activity. The results showed that the antioxidant activity mainly depends on the first and second bond dissociation enthalpies of phenolic hydroxyl groups, the dipole moment and the hydrophobicity descriptors. The antioxidant activity is inversely proportional to the main descriptors. The selected descriptors discriminate the Schiff bases into active and inactive antioxidants.

Hispidin oligomers are styrylpyrone pigments isolated from the medicinal fungi Inonotus xeranticus and Phellinus linteus. They exhibit diverse biological activities and strong free radical scavenging activity. To rationalize the antioxidant activity of a series of four hispidin oligomers and determine the favored mechanism involved in free radical scavenging, DFT calculations were carried out at the B3P86/6-31+G (d, p) level of theory in gas and solvent. The results showed that bond dissociation enthalpies of OH groups of hispidin oligomers (ArOH) and spin density delocalization of related radicals (ArO•) are the appropriate parameters to clarify the differences between the observed antioxidant activities for the four oligomers. The effect of the number of hydroxyl groups and presence of a catechol moiety conjugated to a double bond on the antioxidant activity were determined. Thermodynamic and kinetic studies showed that the PC-ET mechanism is the main mechanism involved in free radical scavenging. The spin density distribution over phenoxyl radicals allows a better understanding of the hispidin oligomers formation.

We have synthesized quinoxaline analogs (1–25), characterized by 1H-NMR and HREI-MS and evaluated for thymidine phosphorylase inhibition. Among the series, nineteen analogs showed better inhibition when compared with the standard inhibitor 7-Deazaxanthine (IC50 = 38.68 ± 4.42 µM). The most potent compound among the series is analog 25 with IC50 value 3.20 ± 0.10 µM. Sixteen analogs 1, 2, 3, 4, 5, 6, 7, 12, 13, 14, 15, 16, 17, 18, 21 and 24 showed outstanding inhibition which is many folds better than the standard 7-Deazaxanthine. Two analogs 8 and 9 showed moderate inhibition. A structure-activity relationship has been established mainly based upon the substitution pattern on the phenyl ring. The binding interactions of the active compounds were confirmed through molecular docking studies.

β-glucuronidase is a lysosomal glycosidase enzyme which catalyzes the extracellular matrix of cancer and normal cells and the glycosaminoglycans of the cell membrane, which is important for cancer cell proliferation, invasion, and metastasis. Liver cancer, colon carcinoma, and neoplasm bladder are triggered by the increase of the level of β-glucuronidase activity. The most valuable structures are indole and oxadiazole which has gain immense attention because of its pharmacological behavior and display many biological properties. Twenty-two (1–22) analogs of indole based oxadiazole were synthesized and screened for their inhibitory potential against β-glucuronidase. Majority of the compounds showed potent inhibitory potential with IC50 values ranging between 0.9 ± 0.01 to 46.4 ± 0.9 µM, under positive control of standard drug d-saccharic acid 1,4 lactone (IC50 = 48.1 ± 1.2 µM). Structural activity relationship (SAR) has been established for all synthesized compounds. To shed light on molecular interactions between the synthesized compounds and β-glucuronidase, 1, 4, and 6 compounds were docked into the active binding site of β-glucuronidase. The obtained results showed that this binding is thermodynamically favorable and β-glucuronidase inhibition of the selected compounds increases with the number of hydrogen bonding established in selected compound-β-glucuronidase complexes.