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In efforts to develop lead anti-TB compounds, a novel series of 19 pyrrolyl benzohydrazides were synthesized and screened to target enoyl-ACP reductase enzyme, which is one of the important enzymes involved in type II fatty acid biosynthetic pathway of M. tuberculosis . Pharmacophores were constructed using GALAHAD to generate alignment of data sets and calculated by Pareto ranking. The pharmacophore features were then filtered by Surflex-dock study using enoyl ACP reductase from M. tuberculosis . Compounds 5b and 5d showed H-bonding interactions with Tyr158, Thr196 and co-factor NAD + that fitted well within the binding pocket of InhA. All the synthesized compounds were screened for preliminary antibacterial activities against Gram-positive S. aureus and Gram-negative E. coli and M. tuberculosis H 37 Rv to evaluate their antitubercular activities. Some representative compounds were further tested for mammalian cell toxicity using human lung cancer cell-line (A549) that was found to be nontoxic. These compounds exhibited moderate inhibition activities against InhA. [ABSTRACT FROM AUTHOR]

Novel pyrrolyl hydrazones and their copper complexes have been synthesized and characterized using analytical and spectral techniques to show the tetrahedral geometry for Cu(II) complexes. Biological activities of hydrazones have been assessed to understand the role of metal ion on their biological activity and the effect of pyrrolyl hydrazones. In vitro antitubercular activity against Mycobacterium tuberculosis of the metal complexes ( 13b and 13r ) exhibited the highest antitubercular activity that are quite close to rifampicin (0.4 μg/mL), giving a MIC of 0.8 μg/mL. All other compounds showed good activity with the MIC values ranging from 1.6 to 100 μg/mL. A comparative study of inhibition values of the ligands and their complexes showed higher antimicrobial activity of the complexes than the ligands. Some compounds have a good activity against InhA and in particular, compounds 12r , 13b and 13r exhibited more than 60% binding with the enzyme even at 5 μM (exhibited good IC50 upto 2.4 μM). Most of the active molecules have a very less cytotoxicity against the human lung cancer cell-line A549. The docking and 3D-QSAR studies have been carried out to provide some insights into the mechanism of action for this class of compounds. [ABSTRACT FROM AUTHOR]

We report here the synthesis, antibacterial and antitubercular evaluation of 61 novel pyrrolyl derivatives bearing pyrazoline, isoxazole and phenyl thiourea moieties. Molecular docking was carried out on enoyl ACP reductase from Mycobacterium tuberculsosis using Surflex-Dock, which is one of the key enzymes involved in type II fatty acid biosynthetic pathway of Mycobacterium tuberculosis , an attractive target for designing novel antitubercular agents. Docking analysis of the crystal structure of ENR performed using Surflex-Dock in Sybyl-X 2.0 software indicates the occupation of substituted pyrrolyl derivatives into hydrophobic pocket of InhA enzyme. Compounds 9b and 9d exhibited the highest antitubercular activity almost close to isoniazid (0.4 μg/mL) with a MIC value of 0.8 μg/mL. All other compounds showed the good activity with a MIC value of 6.25–100 μg/mL. The compounds were further tested for mammalian cell toxicity using human lung cancer cell-line (A549) and were nontoxic. Some compounds exhibited inhibition activities against InhA. [ABSTRACT FROM AUTHOR]

A new series of pyrrolyl phenoxy derivatives bearing alkoxy linker were synthesized and evaluated for anti-tubercular activity (anti-TB) against Mycobacterium tuberculosis . Molecular modeling, pharmacophore constructed using GALAHAD to produce an effective alignment of data set and evaluated by Pareto ranking. The pharmacophore features were filtered by Surflex-dock study using enoyl ACP reductase from M. tuberculosis , which is one of the key enzymes involved in type II fatty acid biosynthesis pathway of M. tuberculosis . Compound 6a27 showed the H-bond with NAD + , whereas compound 6a26 showed H-bonds with Tyr158, Thr196, Met199 and NAD + that fitted well into the binding pocket of target InhA. The alkoxy linker bridge and acceptor groups with benzene ring were advantageous for anti-TB activity, which merit further investigation. [ABSTRACT FROM AUTHOR]

Abstract: In order to develop a lead antimycobacterium tuberculosis compound, a series of 52, novel pyrrole hydrazine derivatives have been synthesized and screened which target the essential enoyl-ACP reductase. The binding mode of the compounds at the active site of enoyl-ACP reductase was explored using surflex-docking method. The binding model suggests one or two hydrogen bonding interactions between pyrrole hydrazones and InhA enzyme. Highly active compound 5r (MIC 0.2 μg/mL) showed hydrogen bonding interactions with Tyr158 and NAD+ in the same manner as those of ligands PT70 and triclosan. The CoMFA and CoMSIA models generated with database alignment were the best in terms of overall statistics. The predictive ability of the CoMFA and CoMSIA models was determined using a test set of 13 compounds, which gave predictive correlation coefficients (r pred 2) of 0.896 and 0.930, respectively. [Copyright &y& Elsevier]

[Display omitted] In the present study, dopamine interaction with bovine serum albumin was investigated using fluorescence, UV–vis, Raman, CV, FTIR and molecular modeling techniques. The fluorescence study of the quenching was carried out at an excitation wavelength of 296.0 nm, and the emission was measured in the range of 300–600 nm. BSA was quenched through both static and dynamic mechanisms. Thermodynamic parameters were derived to study the binding forces involved. The average binding distance between BSA and dopamine was determined using FÖrsters theory. Lifetime measurements, synchronous fluorescence and 3D spectra supported the hypotheses derived from the fluorescence data. The presence of some common co-existent drugs and the effect of essential biological metal ions were also investigated. [ABSTRACT FROM AUTHOR]

Bacterial infections are increasingly difficult to combat as bacteria evolve resistance to antibiotic drugs and have severely compromised the arsenal of antibiotic drugs. On the other hand matrix metalloproteinases (MMPs) play a fundamental role in inflammation and extracellular matrix degradation in physiological and pathological conditions. In search of potent antibiotic, taking coumarin and dihydropyrimidinone as lead compound, a green, eco-friendly and efficient protocol has been developed and synthesized the dihydropyrimidin-2(1 H )-one/thione derivatives of coumarin 3/4 from substituted 4-formylcoumarins 2 and ethylacetoacetate using urea/thiourea in the presence of catalytic amount of ceric ammonium nitrate is reported. All the synthesized compounds were evaluated for their antibacterial activity against four bacterial strains by broth dilution method. The tested compounds have exhibited promising in vitro potency with low MIC values against the drug susceptive S. aureus strain with low MIC values ranging from 0.2 to 6.25 μg/mL. The in vivo anti-inflammatory potency of 3a–e and 4a–e by gelatin zymography is comparable to that of tetracycline. Molecular docking study performed for all the synthesized compounds with S. aureus DNA gyrase and results obtained were quite promising. [ABSTRACT FROM AUTHOR]

2-Propargylthiobenzimidazole 1 , 4-bromomethyl coumarins/1-aza-coumarins 2 / 3 and sodium azide have been reacted in one pot under Click chemistry conditions to give exclusively 1,4-disubstituted triazoles 5a – n . Anti-tubercular assays against M. tuberculosis (H 37 Rv) coupled with in silico molecular docking studies indicated that dimethyl substituents 5c and 5d showed promising activity with higher C-score values. [ABSTRACT FROM AUTHOR]

• Library of 2,5 and 1,5-Regioisomers of 5-substituted tetrazoles were designed and synthesized. • The compounds were screened for in vitro anticancer and antifungal activity. • All the compounds exhibit good safety profile in HCT-116 colon cancer cell lines. • Amongst all compounds 6h, 6g, 6i have the highest zone of inhibition and 6g, 5f have excellent activity with very low IC 50 values were found as good hits. • Computational toxicity and in silico studies was done for them. A novel series of compounds was synthesized using 3-arylsydnone 1a-b. Initially, 3-arylsydnone was converted into 1-aryl-1 H- pyrazole-3-carbonitriles 2a-b via [3+2] cycloaddition with acrylonitrile by ring transformation which once again underwent [2+3] cycloaddition with sodium azide to afford 5-(1-aryl-1 H -pyrazol-3-yl)-1 H -tetrazoles 3a-b.These were subjected to N-alkylation with 4-bromomethyl coumarins 4c-e to afford regioisomers viz., 2,5- and 1,5-disubstituted tetrazole derivatives 5f-k and 6f-k. Single crystal X-ray analysis of compound 6f was carried out. All the synthesized compounds were characterized using various techniques including 1H NMR, 13C NMR, FT-IR, elemental analysis, and mass spectroscopy.These previously unknown compounds were screened for their anticancer activity against HCT-116 colon cancer and non-cancerous L929 cell line at a single high dose (10−5 M) concentration assay. Among the tested compounds, 6g and 5f have exhibited excellent activity with very low IC 50 value i. e.,27.85 µg/mLand 37.86 µg/mL respectively, comparable with standard Cisplatin. In the non-cancerous L929 cell line, the tested compound 6f was proven to be less toxic, and all the tested compounds exhibited toxicity at higher concentrations comparable with standard Cisplatin. Further, the in vitro antifungal activity against Candida albicans for these compounds 5f-k and 6f-k revealed potential to moderate activities compared to the standard. Moreover, docking analysis was performed to know the exact binding mode of the newly synthesized compounds with N- myristoyltransferase (PDB ID: 1IYL) from Candida albicans which was selected as the antifungal targets. The drug-likeness of the compound was assessed using Molinspiration, while the toxicity profile was evaluated using Protox. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Two series of 4-aryloxymethyl coumarins derived from the reaction of 4-bromomethyl coumarins with ethyl gallate and ethyl ester of N-Benzoyl tyrosine have been synthesized. Gallate ethers 3a–3g and tyrosine derivatives 4e–4j were most effective against Entercoccus faecalis. They were also found to be effective against Aspergillus niger and Candida albicans. Comparative docking studies with novobiocin have indicated better binding ability and higher ‘C’ score values than novobiocin. [Copyright &y& Elsevier]

• A series of new coumarino-azetidinones (3a-l) were designed and synthesized. • All the compounds were screened for antitubercular and antimicrobial activity. • Compounds 3e and 3k emerged out as promising antituberculars and antimicrobials. • Compounds 3e and 3k were exhibited comparatively less toxicity. • Excellent molecular docking scores were observed. In the present work, a series of new coumarino-azetidinones (3a-l) were designed, synthesized and evaluated for biological activities. The newly synthesized compounds (3a-l) were fully characterized by several spectroscopic techniques and elemental analyses. The synthesized compounds (3a-l) were screened for their preliminary in-vitro antitubercular and antimicrobial activities. Almost all the coumarino-azetidinones showed promising activity against Mycobacterium tuberculosis (M. tuberculosis) H 37 Rv strain. Conversely, some of the coumarino-azetidinones displayed interesting antimicrobial activities. Moreover, most active compounds were tested for cytotoxicity studies and exhibited low-level cytotoxicity towards Vero cells. Last but not the least, molecular docking results showed excellent interactions with M. tuberculosis InhA-D148G mutant (PDB. 4TZK) and Escherichia coli (E. coli) (PDB. 4JX8). The results of biological evaluation suggest that the coumarino-azetidinones are promising lead compounds for the subsequent investigation in search of new antitubercular and antimicrobial agents. Image, graphical abstract In the present study, a series of new coumarino-azetidinones were synthesized, characterized and evaluated for their preliminary antitubercular, antimicrobial and cytotoxicity activity. [ABSTRACT FROM AUTHOR]

The six-membered ring heterocycle 1,3,5-triazine and its derivatives have attracted considerable attention as they have proven to be excellent bioactive herbicides, cancer agents, etc. A series of 1,3,5-triazine derivatives (3a-o) were synthesized by a single step reaction and characterized by 1H NMR, 13C NMR, and mass spectrometry analysis. Antimicrobial screening of title compounds (3a-o) was examined against five bacterial and two fungal strains. In vitro study revealed that the freshly synthesized 6-(thiazol-4-yl)-1,3,5-triazine-2,4-diamine (3o) showed good antibacterial growth inhibition against E. coli , K. pneumoniae , and A. baumannii bacterial strains, and even the fungi C. neoformans. Molecular docking studies were performed on the X-ray crystal structure of E. coli 24 kDa domain in complex with clorobiocin (PDB code: 1KZN; resolution 2.30 Å) using Surflex-Dock program of Sybyl-X software. The results obtained are very encouraging. Image 1 • A simple method for the direct access to 1,3,5-triazines is documented. • Good functional group tolerance, including one fluorinated compound. • Excellent molecular docking scores were observed. • Broad biological screening for both bacteria and fungi are reported. • Compound (3o) showed good antimicrobial growth inhibition. [ABSTRACT FROM AUTHOR]

• Cyclic ureido based mono/ bis -coumarin 'click triazoles' have been synthesized. • Newly synthesized triazoles inhibited Mycobacterium tuberculosis H37Rv. • Benzimidazolono- bis -coumarinyl triazoles exhibited lower MIC values. • Theophylline/uracil-based mono/ bis -coumarin triazoles exhibited higher MIC values. • Cytotoxicity studies exhibited IC 50 values 10 times higher than Mtb MIC values. Nucleoside bases like uracil, pharmacophoric triazoles and benzimidazolones have been used during the present study to design molecular matrices for antitubercular activity, employing Click Chemistry. Click triazoles 4 / 7 / 10 have been obtained by the reaction of 4-(Azidomethyl)-2 H -chromen-2-ones/quinolin-2(1 H)-ones 3 and propargyl ethers 2/6/9 derived from theophylline/6-methyl uracil/2-benzimidazolone respectively. In addition to spectral data structures have been confirmed by single crystal X-ray diffraction studies in case of uracil bis alkyne (6) and theophylline mono triazole (4c). Theophylline linked mono triazoles, 4 (a-d) and 6-methyl uracil linked bis triazoles, 7 (a-e) have been found to inhibit Mycobacterium tuberculosis H37Rv with MIC values in the range 55.62–115.62 μM. Benzimidazolone bis triazoles, 10 (a-n) showed better activity with MIC in the range 2.33–18.34 μM. Molecular modeling studies using Surflex-Dock algorithm supported our results. [ABSTRACT FROM AUTHOR]

A series of novel 5-(1-aryl-3-(thiophen-2-yl)-1 H -pyrazol-4-yl)-1 H -tetrazoles 7 ( h-s ) were designed and synthesized. Structural characterization was done by spectral and single crystal X-ray studies. The intermolecular interactions of compound 7n were quantified and visualized using Hirshfeld surface analysis. Structures of newly synthesized compounds were docked into active site of COX-2 enzyme PDB: 1CX2 , 3.0 Å X-ray resolution and plausible binding modes were compared with standard drug Celecoxib . The results of molecular docking prompted the pharmacological studies for further optimization of identified selective inhibition. The compounds 7k , 7m , 7n , and 7q-s have shown excellent anti-inflammatory activity and compounds 7i , 7k , 7l , 7n , and 7s have exhibited anti-bacterial inhibitory potency in enzyme based assays. [ABSTRACT FROM AUTHOR]

A series of novel coumarin-theophylline hybrids were synthesized and examined for their anti-tubercular activity in vitro against Mycobacterium tuberculosis H 37 Rv, anti-microbial activity in vitro against gram-positive bacteria ( Staphylococcus aureus ) and gram-negative bacterias ( Escherichia coli , Salmonella typhi ) as well as fungi ( Candida albicans ). The compound ( 3a ) has shown excellent anti-tubercular activity with MIC of 0.12 μg/mL. Electron donating compounds ( 3a, 3f ) have displayed significant anti-microbial activity. The compounds have also been precisely elucidated using single crystal X-ray diffraction techniques. Molecular docking study has been performed against 4DQU enzyme of Mycobacterium tuberculosis showed good binding interactions and is in agreement with the in vitro results. [ABSTRACT FROM AUTHOR]

A green and efficient protocol has been developed and a series of coumarin based pyrano[3,2- c ]chromene derivatives ( 2 ) have been synthesized using multi-component reaction (MCR) approach. Unexpected 3-coumarinyl-3-pyrazolylpropanoic acids ( 3 ) and C 4 -C 4 chromenes ( 5 ) have been isolated instead of expected product 4 by the reaction of compound ( 2 ) in formic acid at 90 °C for about 4–5 h and at 130 °C for about 8–10 h respectively. Further, C 4 -C 4 chromenes ( 5 ) formation was confirmed by intramolecular cyclization of compounds ( 3 ). These compounds were screened for their biological activities and most of them exhibited promising antibacterial activity. The anti-inflammatory assay was evaluated against HRBC membrane stabilization method and the compounds exhibit excellent anti-inflammatory activity. Molecular docking study has been performed for all the synthesized compounds with Klebsiella pneumoni ae acetolactate synthase and results obtained are quite promising. [ABSTRACT FROM AUTHOR]

We report herein, first ever synthesis of series of novel differently substituted quinoxalinyl chalcones using Claisen Schmidt condensation, its molecular docking studies, and potential to be good anti-microbial, anti-tubercular and anti-cancer agents. The antimicrobial studies were carried out against Staphylococcus aureus , Escherichia coli and Candida albicans using disc diffusion procedure. The selected chalcones were tested for anti-cancer and cytotoxicity activity against MCF-7 cancer cell line using MTT assay method. All the synthesized compounds were screened for in vitro anti-tubercular screening against MtbH37RV strains by Alamar blue dye method. These results were compared with molecular docking studies carried out on Mycobacterium tuberculosis enzyme enoyl ACP reductase using Surflex-Dock program that is interfaced with Sybyl-X 2.0. SAR analysis for antimicrobial and antitubercular activity has also been proposed. [ABSTRACT FROM AUTHOR]

Transition metal coordination complexes of Co(II), Ni(II), Cu(II) and Zn(II) with a newly designed ligand, 2-(2-(1H-benzo[d]imidazol-2-yl)hydrazono)propan-1-ol have been synthesized and characterized using various spectro-analytical techniques. The molecular structures of Co(II), Cu(II) and Zn(II) complexes are determined by single-crystal X-ray diffraction method. The metal to ligand stoichiometry has been found to be 1:2 in the case of Cobalt(II), Nickel(II) and Zinc(II) whereas 1:1 in the case of Copper(II) complex. The newly synthesized ligand and complexes have been assessed for their growth inhibiting potencies against H37Rv strain of Mycobacterium tuberculosis . The copper and cobalt complexes have emerged to be potent in vitro growth inhibitors of H37Rv. All the complexes are inhibiting the growth of other tested common microbial flora to a significantly lesser extent, making them selective towards H37Rv in the preliminary analysis. The consensus scores obtained by the docking studies of the molecules to the target protein enoyl acyl carrier protein reductase of M. tuberculosis H37Rv are in good agreement with the obtained MIC values. [ABSTRACT FROM AUTHOR]

A new series of 2,5 and 1,5-regioisomers of the tetrazolyl group viz ., 3-[(5-benzyl/benzylthio-2 H -tetrazol-2-yl) methyl]-2-chloro-6-substituted quinoline 6h-q and 3-[(5-benzyl/benzylthio-1 H -tetrazol-1-yl) methyl]-2-chloro-6-substituted quinolines 7h-q were synthesized. Docking studies of all these compounds with DNA as target using PDB: 1AU5 and 453D revealed that the compounds 6h and 6i act as covalent cross linker on the DNA helix of the former and intercalate the latter both with higher C score values. Another set of docking studies in the active pocket of dihydrofolate reductase and N -myristoyl transferase as targets to assess antifungal activity revealed that compounds 6k , 6l , 6p and 7q (with bromo and fluro substituents) showcases different binding modes and hydrogen bonding. Further, the compounds were screened for anticancer activity (primary cytotoxicity) against NCI-60 Human tumor cell line at a single high dose (10 −5 M) concentration assay. Among the tested compounds, 6h has shown 99.28% of GI against Melanoma (SK-MEL-5) and compound 6i has shown 97.56% of GI against Breast Cancer (T-47D) . Further, in vitro antifungal assay against A. fumigatus and C. albicans for these compounds 6h-q and 7h-q revealed potential to moderate activities as compared to the standard. [ABSTRACT FROM AUTHOR]

A green, eco-friendly and efficient protocol has been developed and synthesized a series of coumarin based pyrano[2,3- c ]pyrazole derivatives ( 3 ) by multi-component reaction (MCR). Unexpected 3-coumarinyl-3-pyrazolylpropanoic acids ( 4 ) have been isolated by the reaction of compound ( 3 ) in acidic conditions. Further, intramolecular cyclization of compounds ( 4 ) leads to C 4 C 4 chromons ( 9 ) and these compounds were screened for their biological activities using array of techniques. Most of the compounds exhibited promising antibacterial activity, in particular Gram-positive bacteria. The anti-inflammatory assay was evaluated against protein denaturation as well as HRBC membrane stabilization methods and compounds exhibit excellent anti-inflammatory activity in both methods. Molecular docking study has been performed for all the synthesized compounds with S. aureus dihydropteroate synthetase (DHPS) and results obtained are quite promising. [ABSTRACT FROM AUTHOR]

• Simple synthetic procedures were employed to synthesize new triazole bridged bi-heterocycles. • Synthesized scaffolds were assessed for their in vitro antitubercular, antioxidant, cytotoxic and superoxide dismutase enzyme activities. • The scaffolds were proven to be potential anti-TB agents. • Molecular docking studies with DprE1 enzyme shown similar interaction of compounds as that of FDO ligand. • The scaffolds may be considered for in vivo use as lead drug. In search of new potent molecules against tuberculosis, 3,4-dihydro-2(1H)-quinolinone based 1,2,3-triazoles were synthesized efficiently by means of click chemistry and their structures were confirmed by spectral data. Among the synthesized twelve novel molecules, seven are hybrid of 3,4-dihydro-2(1H)-quinolinone, 1,2,3–1H-triazole nucleus with different coumarin derivatives and in remaining molecules coumarin is replaced by alkyl, aryl, and pyranose derivatives. Among the synthesized compounds, eight were screened for anti-TB activity against H37Rv strain and found to have good inhibition activity with lower MIC values (2.7–10.6 µM). Compound 6 h with (6-(acetoxymethyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate) substitution is most active against MTB. Further their antioxidant activity was assessed using DPPH assay and the compounds have shown moderate to low activity compared to standard ascorbic acid. The cytotoxicity of the synthesised compounds against lung cancer cell lines exhibited good to moderate activity and do not induce significant toxicity. In Superoxide dismutase(SOD) enzyme activity studies some of the compounds exhibited promising activity. The interactions of the molecules were studied against DprE1 protein of MTB through molecular docking. [Display omitted] [ABSTRACT FROM AUTHOR]

• Novel coumarin-thioether conjugates were synthesised and characterised. • The synthesised compounds are assessed for in vitro anti-TB activity (H 37 Rv strain). • Compound 6b (MIC = 0.39 µg/mL) was twofold more active than Rifampin (0.8 µg/mL). • Compounds 6b and 6f possessed low level of cytotoxicity against Vero cells. • Molecular docking study revealed higher C-score values that supports the findings. In this work, we report a series of 4-(2,6-dimethylphenyl)thio)methyl)-2H-chromen-2-one conjugates as promising leads to treat tuberculosis. Spectroscopic and other analytical methods were used to validate the synthesised compounds. The compounds were assessed for in vitro anti-tubercular activity with the H 37 Rv strain of Mycobacterium tuberculosis. Further, cytotoxicity studies were performed using Vero cells. Most of the synthesised conjugates were effective and displayed notable activity with MIC values in the range 0.39–12.5 µg/mL.The most diligent compound 6b (MIC = 0.39 µg/mL) was twofold more active than standard anti-TB drug Rifampin (0.8 µg/mL) and was comparable to Isoniazid (0.1 µg/mL). Compound 6f also displayed exemplary activity (MIC 0.78 µg/mL). Both compounds 6b and 6f possessed low levels of cytotoxicity, Molecular docking evaluation of the synthesised conjugates and 4DQU ligand demonstrated that the synthesised conjugates had higher C-score values that further supports the obtained results. It indicates compound 6b and 6f are promising lead compounds in search of novel antitubercular drug-like molecules. [Display omitted] [ABSTRACT FROM AUTHOR]

A series of mono and bis -triazole coumarin hybrids 6a–u and 9a–f respectively have been synthesized using 4-(azidomethyl)-2 H -chromen-2-ones 5a–i and aryl propargyl ethers 2a–c/8 employing Click chemistry modified protocol for Azide-Alkyne cycloadditions(CuAAC). Anti-tubercular screening showed moderate activity for mono aryloxy compounds 6a–u with MIC 50–100 μg/mL, whereas the bis compounds 9a–f were more effective with MICs between 0.2 and 12.5 μg/mL. Molecular modeling and 3D-QSAR measurements using CoMFA and Topomer CoMFA further supported the observed results. The bis compound 9b showed excellent activity with MIC value as low as 0.2 μg/mL. [ABSTRACT FROM AUTHOR]

• Novel quinoline containing 3-piperazin-1-yl-benzo[ d ]isothiazole and 3-piperidin-4-yl-benzo[ d ]isoxazoles were synthesized. • The single crystal XRD, DFT studies and in silico pharmacokinetic and toxicity parameters were done. • In vitro antimicrobial activity was analysed and correlated with energy difference in Frontier Molecular Orbitals. • Antimicrobial activity observed from in vitro assays and DFT studies were validated by Docking studies. Novel quinoline containing 3-piperazin-1-yl-benzo[ d ]isothiazole 4a and 4b and 3-piperidin-4-yl-benzo[ d ]isoxazole 5c were synthesized and characterized by spectral, single crystal XRD and DFT studies. Hirshfeld surface, electrostatic potential maps were obtained respectively from SCXRD and DFT studies. These compounds were analysed for in vitro antimicrobial activity and correlated with energy difference (ΔE) between HOMO and LUMO energy levels obtained from DFT and correlated with ΔE of standard drug to explain the activity. Further the antimicrobial activity was corroborated by docking against various target enzymes. The present work provided some hints for developing novel antimicrobial quinoline derivatives. [Display omitted] [ABSTRACT FROM AUTHOR]

• Anticancer drugs have achieved great successes in recent years. • Designed and synthesized dipyrromethane-coumarin and porphyrin-coumarin Derivatives. • Dipyrromethane-coumarins and porphyrin-coumarins were screened for their anticancer activity at NCI-USA. • Among the synthesized series, two compounds were referred three time repeat analysis and three time recommended to Biological evaluation committee (BEC) in NCI. These two compounds are most prominent anticancer agents with GI 50 values <1. 0 µM. Coumarin analogues of dipyrromethane and porphyrin derivatives were synthesized and tested for their in-vitro anticancer activity at NCI (USA). Seven of the obtained compounds, 4-(di(1H-pyrrol-2-yl)methyl)-6-methoxy-2H-chromen-2-one (2c), 4-((1H-pyrrol-2-yl)(2H-pyrrol-2-ylidene)methyl)-6-methyl-2H-chromen-2-one (3a), 4-((1H-pyrrol-2-yl)(2H-pyrrol-2-ylidene)methyl)-6-chloro-2H-chromen-2-one (3d), Tetrahydro(6-methyl-coumarin) calix [4]pyrroles (4a), Tetrahydro(6-methoxy-coumarin) calix [4]pyrroles (4c), Tetra(6-methyl-coumarin) calix [4]pyrroles (5a) and Tetra(6-methoxy-coumarin) calix [4]pyrroles (5c) were screened for their antiproliferative activity against 60 human cancer cell lines. Among seven selected compounds, 2c, 3a, 4a and 4c showed remarkable activity with GI 50 values around 1. 0 μM (54 out of 60 cell lines) and <1. 0 μM (59 out of 60 cell lines) respectively. Interestingly, two compounds 2c and 4a have been subjected more than three times for repeat analysis against all the 60 cell lines and have been referred to Biological Evaluation Committee (BEC) for their advance study, among these two, compound 2c has been referred to BEC three times. Further, the ct-DNA interaction, absorptions and fluorescence quenching results of more active compounds 2c and 4a are quite promising. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel coumarin-4-yl-1,3,4-oxadiazolyl-2-mercaptobenzoxazoles 8i-t are reported. • Microwave synthesis resulted shorter reaction times, excellent yields with high purity. • The reported compounds demonstrated high selectivity against COX-2. • All the compounds exhibited strong antioxidant activity. A modest, competent and green synthetic procedure for novel coumarinyl-1,3,4-oxadiazolyl-2-mercaptobenzoxazoles 8i-t has been reported. Analysis of the docked (PDB ID: 5IKR; A-Chain) poses of the compounds illustrated that they adopt identical conformations to the extremely selective COX-2 inhibitor. The biological outcomes as well as computational study suggested that the compounds originated to have elevated resemblance towards COX-2 enzyme than COX-1. The compounds 8i , 8l , 8q , 8r , 8s and 8t emerged as most potent and selective COX-2 inhibitors in contrast with Mefenamic acid. The selectivity index of 8l , 8n and 8r was respectively found to be 33.95, 20.25 and 24.98 which manifested their high selectivity against COX-2. Interestingly, the compounds which were active as COX-2 inhibitors were also active as antioxidant agents. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel quinoline and 1,2,4-triazole appended triazole derivatives were conceived. • Microwave synthesis resulted transitory reaction times, exceptional yields and purity. • The reported compounds proclaimed excellent anti-tubercular activity. • All the compounds exhibited exceptional antifungal activity. Quinolin-3-yl-methyl-1,2,3-triazolyl-1,2,4-triazol-3(4 H)-ones 8j-v were synthesized by click chemistry as an ultimate tactic where [3 + 2] cycloaddition of azides with terminal alkynes has been evolved. Herein, we are inclined to divulge the implication and prevalence of CuSO 4 ·5H 2 O and THF/water promoted [3 + 2] cycloaddition reactions. The foremost supremacy of this method are transitory reaction times, facile workup, excellent yields (88–92%) with exorbitant purity and regioselective single product formation both under conventional and microwave method. Docking studies illustrated strong binding interactions with enzyme InhA-D148G (PDB ID: 4DQU) by means of high C-score values. The anti-tubercular and antifungal screening of synthesized compounds proclaimed promising activity. The in vitro and in silico studies imply that these triazoles appended quinolines may acquire the ideal structural prerequisites for auxiliary expansion of novel therapeutic agents. [ABSTRACT FROM AUTHOR]

• Anticancer and anti-TB activity of novel coumarin-azaspiro conjugates (1a-1l). • 1f exhibited the most potent activity against MDA-MB-231cell line (IC 50 = 9.05 µM). • 1g showed most potent activity against A549 cell line (IC 50 = 7.05 µM). • 1c is found to be the hit candidate against MTBH 37 Rv strain with MIC 0.78 µg/mL. In this work, a series of new 8-[(substituted 2-oxo-2H-chromen-4-yl)methyl]-8-azaspiro[4.5]decane-7,9-dione derivatives (1a - 1l) is synthesized and characterized by 1H NMR, 13C NMR, FT-IR, GC-MS and elemental analysis. In addition, the structure of compound 1k has been elucidated using single crystal X-ray diffraction techniques. The synthesized compounds are screened for their anticancer and anti-TB activity. Preliminary anticancer results showed that compounds (1a - 1l) exhibit moderate to potent activity against MDA-MB-231, A549, HT-29 and Hela cancer cell lines. Compound 1f exhibited the most potent activity against MDA-MB-231cell line with IC 50 value of 9.05 µM concentration, compound 1g and 1h showed potent activity against A549 cell line with IC 50 value of 7.05 and 13.31 µM concentration respectively. Compound 1j showed good cytotoxicity against Hela cell line with IC 50 of 16.14 µM, whereas, compound 1l is found to be moderately active against HT-29 cell line with IC 50 of 18.07 µM. Anti-tubercular activity revealed that compound 1c, 1d, 1g, 1h and 1j have significant activity against MTBH 37 Rv strain with MIC 0.78, 1.56, 0.19, 0.39 and 0.78 µg/mL respectively. Further, to investigate the mechanism of anti-TB activity and detailed intermolecular interactions between the synthesized compounds, molecular docking studies are performed. [ABSTRACT FROM AUTHOR]

The enzymes MetAP-2 and NMT play a crucial role in the process of myristoylation of oncoproteins which is deregulated in many types of cancers. Execution of both these enzymes is considered as strategy for the intervention of various cancers and relative fungal infections, and hence the discovery of novel MetAP-2 and NMT inhibitors necessitate their high relevancy. In this investigation, we have synthesized a series of novel seven-membered triazolothiadiazepinyl quinolines 10(a – m) distinctively under microwave irradiation technique and identified as selective MetAP-2 and NMT inhibitors. Amongst the functionalized derivatives when evaluated for the in vitro antifungal assay, compounds 10b , 10c , 10e and 10f were considered promising due to notable inhibitory effects (MIC = 0.2 mg/mL) on Aspergillus fumigatus. Screening of the anticancer activity against NCI-60 Human tumor cell lines portrayed that conjugates 10b , 10c , 10e and 10f were found to be moderately effective against the Renal Cancer cell line UO-31. The data acquired from biological studies was further validated by molecular docking studies and pharmacokinetic evaluation. Image 1 • Microwave-assisted synthesis of triazolothiadiazepinyl quinolines was achieved. • Triazolothiadizepinylquinoline analogues were identified as MetAP-2/NMT inhibitors. • 10b , 10c , 10e & 10f exhibited anticancer activity on Renal Cancer cell line UO-31. • 10b , 10c , 10e & 10f are promising antifungals against Aspergillus fumigatus. • 10b , 10c , 10e & 10f exerted vital potency against MetAP-2/NMT verified by docking. [ABSTRACT FROM AUTHOR]