Microwave assisted synthesis of coumarin-purine derivatives: An approach to in vitro anti-oxidant, DNA cleavage, crystal structure, DFT studies and Hirshfeld surface analysis.

An easy and efficient microwave-assisted protocol has been developed for the synthesis of coumarin-purine hybrids (3a-3j). The newly constructed 1,3-dimethyl-7-((substituted)-2-oxo-2H-chromen-4-yl)methyl)-1H-purine-2,6(3H,7H)-dione derivatives were evaluated for their in vitro antioxidant activity by DPPH free radical-scavenging ability assay and DNA cleavage by using calf thymus. The compound 3i, shows the most excellent DPPH scavenging activity with a -OH substitution at C7 of coumarin ring. In addition, the structure of compound 3f, has been elucidated using single crystal X-ray diffraction technique. Theoretical calculations (DFT) were carried out using Gaussian09 program package and B3LYP correlation function. Full geometry optimization were carried out using 6-311G++(d, p) basis set and the frontier orbital energy were presented. Hirshfeld surface analysis was used for the intermolecular interactions in the crystal structure. The experimental result of the compound 3f has been compared with the theoretical results and it was found that the experimental data are in a good agreement with the calculated values.

Functionalization of 3-chloroformylcoumarin to coumarin Schiff bases using reusable catalyst: an approach to molecular docking and biological studies.

Recently, heterogeneous catalysts have been explored eximiously in the synthesis of heterocyclic compounds. Therefore, here we used solid-supported heterogeneous silica sulfuric acid as a catalyst for the synthesis of Schiff's base of 3-chloroformylcoumarin in view of simplified procedure, reusability and acceptable efficiency, which are required in organic synthesis. An efficient and facile methodology is preferred for synthesis of a class of chromeno-3-substituted derivatives (1a-1l) with good yields. The molecular docking results showed excellent binding interactions with the Mycobacterium tuberculosis InhA-D148G mutant (PDB: 4DQU). The same biomolecules were screened for their in vitro anti-tubercular activity against the M.tb H37Rv strain and antimicrobial studies. Physico-chemistry, toxicity prediction with IC50 value and bioactivity score were also calculated for title compounds. Most active compounds were further tested for cytotoxicity studies and exhibited low-level cytotoxicity against Vero cells. The suggested conjugates are promising lead compounds for the subsequent investigation in search of new anti-tubercular agents. All the conjugates were obtained within the range and followed the Lipinski rule of 5, indicating more 'drug-like' nature.

Microwave-assisted synthesis, computational studies and antibacterial/ anti-inflammatory activities of compounds based on coumarin-pyrazole hybrid.

An efficient, high-yield and rapid synthesis of (E)-1,5-dimethyl-4-((2-((substituted-2-oxo-2H-chromen-4-yl)methoxy)naphthalen-1-yl)methyleneamino)-2-phenyl-1,2-dihydropyrazol-3-one derivatives (3a-3i) containing Schiff base structures under microwave-irradiation has been described. Schiff base is a potential target to discover anti-inflammatory chemotherapeutics, material science, catalysis and molecular magnetism. All the newly synthesized compounds (3a-3i) have been characterized by elemental analysis and spectroscopic techniques. The synthesized compounds (3a-3i) were evaluated for their antibacterial activity by agar-well diffusion method and anti-inflammatory activity by egg albumin denaturation method. The compounds (3e) and (3i) exhibit antibacterial effect with minimum inhibitory concentration (MIC) 0.78 µg ml-1 and MIC 1.562 µg ml-1 against Gram-positive Staphylococcus aureus bacterial strain compared with standard ciprofloxacin drug (MIC 6.25 µg ml-1). The compounds (3c) and (3f) exhibited an inhibition of heat-induced protein denaturation at the concentration (31.25 µg ml-1) as 53.65% and 67.27%, respectively, and these compounds are more active than standard aceclofenac drug (5.50%). Molecular docking study has been performed for all the synthesized compounds with S. aureus dihydropteroate synthetase and results obtained are quite promising.

Molecular docking studies and facile synthesis of most potent biologically active N-tert-butyl-4-(4-substituted phenyl)-2-((substituted-2-oxo-2H-chromen-4-yl)methylthio)-6-oxo-1,6-dihydropyrimidine-5-carboxamide hybrids: An approach for microwave-assisted syntheses and biological evaluation.

An efficient, high yields and rapid synthesis of N-tert-butyl-4-(4-substituted phenyl)-2-((substituted-2-oxo-2H-chromen-4-yl)methylthio)-6-oxo-1,6-dihydropyrimidine-5-carboxamide derivatives (4a-4j) under microwave-irradiation has been described. All the newly synthesized compounds (4a-4j) were characterized by elemental analysis and spectroscopic studies. The synthesised compounds (4a-4j) were evaluated for their antibacterial activity by agar-well diffusion method and anti-inflammatory activity by egg albumin denaturation method. The compound (4f) exhibits antibacterial effect with MIC-2.5 µg/mL against gram positive S. aureus bacterial strain compared to standard ciprofloxacin drug (MIC-10 µg/mL). The compound (4c) shows an inhibition of heat induced protein denaturation 75.42% at a concentration of 31.25 µg/ml and is almost ten times more active than compared to standard aceclofenac drug (5.50%). Molecular docking study has been performed for all the synthesized compounds with S. aureus dihydropteroate synthetase (DHPS) and results obtained are quite promising.

Synthesis of coumarin-theophylline hybrids as a new class of anti-tubercular and anti-microbial agents.

A series of novel coumarin-theophylline hybrids were synthesized and examined for their anti-tubercular activity in vitro against Mycobacterium tuberculosis H37Rv, 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.

Design, synthesis, and evaluation of new α-aminonitrile-based benzimidazole biomolecules as potent antimicrobial and antitubercular agents.

The study explores the one-pot synthesis of novel α-aminonitriles by reacting 4-[(1H-benzimidazol-2-yl)methoxy]benzaldehyde, substituted anilines and sodium cyanide using a catalytic amount of copper dipyridine dichloride (CuPy2 Cl2 ) and employing the Strecker reaction under mild conditions. All the synthesized compounds were screened for antimicrobial and antitubercular activity. The promising lead compounds 4d and 4e were identified, with MIC values ranging between 3.9 and 7.8 µg/mL against different bacterial strains. Compounds 4c-e and 4g also showed good antifungal activities against the tested fungal strain. Among those tested, compound 4e exhibited excellent antitubercular activity (MIC 0.05 µg/mL) with a low level of cytotoxicity, suggesting that compound 4e is a promising lead for subsequent investigations in search for new antitubercular agents.

Design, synthesis of benzocoumarin-pyrimidine hybrids as novel class of antitubercular agents, their DNA cleavage and X-ray studies.

A series of 2-(2-(4-fluorobenzyl)-6-(substituted phenyl) pyrimidin-4-yl)-3H-benzo[f]chromen-3-one derivatives (1a-1o) were selectively prepared in high yields under microwave irradiation. The synthesized compounds were characterized by elemental and spectroscopic analysis; in addition the structures of compound (1a), (1b) and (1j) were elucidated by the X-ray diffraction technique. Compounds (1a-1o) were evaluated for their in-vitro antitubercular activity while the most active compounds were further subjected for their cytotoxicity and DNA cleavage study. Results revealed that most of the tested compounds displayed potent antitubercular activity with MIC in the range 0.05-2.81 µg/mL. Among them, compound (1b) possessed excellent activity (MIC 0.05 µg/mL) against M.tb H37Rv strain and exhibited low level of cytotoxicity against Vero cells, which suggested compound (1b) is a promising lead for subsequent investigation in search of new antitubercular agents. DNA cleavage by gel electrophoresis method revealed that compounds (1b, 1g, 1k and 1n) were found to cleave the DNA completely.

Synthesis and in-vivo evaluation of carbonyl-amide linkage based new benzimidazole derivatives.

In search of pharmacologically active potent compounds, a series of carbonyl-amide linkage based new benzimidazole derivatives were synthesized from acid, aldehydes and isocyanide at ambient temperature via Passerini reaction. All the compounds synthesized were screened for their potential anti-inflammatory, antidiabetic and anticonvulsant properties. The results revealed that compounds 2i and 2j were found to be the most potent anti-inflammatory agents, while compounds 2a, 2c, 2e, 2f, 2i and 2j showed increased antidiabetic activity than the reference drugs and 2a, 2g, 2h, 2i and 2j were found to be the main structural requirement for maintaining anticonvulsant activity.

Synthesis of 2-mercaptobenzimidazole derivatives as potential anti-microbial and cytotoxic agents.

A series of novel 2-(1H-benzimidazol-2-ylsulfanyl)-N-(4-oxo-2-phenyl-thiazolidin-3yl)-acetamide 5a-j have been synthesized from various aldehydes and 2-(5-phenyl-[1,3,4]-oxadiazol-2-ylmethylsulfanyl)-1H-benzimidazole 6a-j from various benzoic acids. These compounds were screened for their in-vitro anti-bacterial activity against Staphylococcus aureus and Enterococcus faecalis as Gram positive, Klebsiella pneumoniae and Escherichia coli as Gram negative bacterial strains and for in-vitro anti-fungal activity against Asperigillus fumigatus and Candida albicans. The in vitro cytotoxic properties were studied using brine shrimp bioassay. Results revealed that, compounds 5b, 5d, 5g, 5i, 6b, 6e, 6f, and 6i showed excellent activity against a panel of microorganisms. The cytotoxic activities of 5b, 5g, 5i, 6b, 6f, 6h, and 6i were found to be good. All the newly synthesized compounds were characterized by elemental analysis, IR, (1)H-NMR, (13)C-NMR and MS.

Analgesic, anti-pyretic and DNA cleavage studies of novel pyrimidine derivatives of coumarin moiety.

A novel series of 4-[4-(6-phenyl-pyrimidin-4-yl)-phenoxymethyl]-chromen-2-ones [5-7(a-e)] were synthesized from various 4-bromomethyl coumarins 1(a-e). The synthesized compounds were screened for in-vivo analgesic and anti-pyretic activities at a dose of 25 and 100 mg/kg body weight (b.w), respectively. Among them, compounds 5(d), 6(c) and 7(d) exhibited significant analgesic activity comparable with standard drug analgin using Tail-flick model. Compounds 5(a) and 7(a-d) showed significant anti-pyretic activities comparable with standard drug aspirin using yeast-induced pyrexia model. DNA cleavage study by agarose gel electrophoresis method was also studied. Qualitative SAR studies indicate that, compounds with amino group at 2-position of pyrimidine ring enhances analgesic and anti-pyretic activities and compounds with hydroxyl and thio group at 2-position of pyrimidine ring increase DNA cleavage activities.

Synthesis, in-vitro antimicrobial and cytotoxic studies of novel azetidinone derivatives.

Developing novel antimicrobial drugs is increasingly important in the modern pharmaceutical industry. A series of novel 3-chloro-4-[4-(2-oxo-2H-chromen-4-ylmethoxy)phenyl]-1-phenylazetidin-2-ones 5a-o have been synthesized from 4-bromomethylcoumarins 1a-e and 4-aryliminomethyl-phenols 3a-c. These compounds were screened for their in-vitro antibacterial activity against two Gram-positive (Staphylococcus aureus and Vancomycin resistant enteroccoccus) and two Gram-negative (Escherichia coli and Shigella dysentery) bacterial strains and antifungal activity against Aspergillus fumigatus, Candida albicans, and Penicillium. Results revealed that compounds 5c, 5f, 5h, 5j, and 5m showed excellent activity against a panel of microorganisms. The brine-shrimp bioassay was also carried out to study their in-vitro cytotoxic properties and two compounds, 5h and 5m, possessing LD(50) = 7.154x10(-4 )M and 5.782x10(-4) M, respectively, displayed potent cytotoxic activity against Artemia salina. The presence of a chlorine group in the coumarin moiety, its effect on their antibacterial, antifungal, and cytotoxic activities is discussed. All newly synthesized compounds were characterized by elemental analysis, IR, (1)H-NMR,( 13)C-NMR, and MS.

Derivatives of benzimidazole pharmacophore: synthesis, anticonvulsant, antidiabetic and DNA cleavage studies.

In seeking broad spectrum pharmacological activities of benzimidazole derivatives, a group of 4-thiazolidinones 5(a-j) and 1,3,4-oxadiazoles 6(a-j) containing 2-mercapto benzimidazole moiety were synthesized and screened for in vivo anticonvulsant activity by Maximal Electroshock (MES) model and antidiabetic activity using Oral Glucose Tolerance Test (OGTT). Compounds (5c), (5d), (5g) and (5i) exhibited potent anticonvulsant results and (6c), (6d), (6h) and (6i) showed excellent antidiabetic activities and also pharmacophore derived from active molecules suggested that presence of -OH group was a common feature in all active compounds. In DNA cleavage studies, compound (5d) cleaved DNA completely as no trace of DNA was found. On the other hand, a sharp streak was found for compounds (5c), (6a) and (6d).

In-vivo analgesic and anti-inflammatory activities of newly synthesized benzimidazole derivatives.

A series of 2-methylaminobenzimidazole derivatives (1-11) were synthesized by the reaction of 2-(chloromethyl)-1H-benzimidazole derivatives with primary aromatic amines. All these compounds were characterized by IR, 1H NMR, 13C NMR, GC-MS and elemental analysis. The newly synthesized compounds were screened for analgesic and anti-inflammatory activities on acetic acid induced writhing in mice and carrageenan induced paw oedema in rats. Compounds (7) and (2) showed a potent analgesic (89% at 100 mg/kg b.w) and anti-inflammatory (100% at 100 mg/kg b.w) activities compared with standard drug Nimesulide (100% at 50 mg/kg b.w) respectively. The other compounds showed good analgesic and anti-inflammatory activities.

2-Azetidinone derivatives: design, synthesis, in vitro anti-microbial, cytotoxic activities and DNA cleavage study.

A novel series of 3-chloro-4-[4-(2-oxo-2H-chromen-4-ylmethoxy)-phenyl]-1-phenyl-azetidin-2-one derivatives (5a-j) have been synthesized from 4-aryloxymethylcoumarins (1a-e) and 4-aryliminomethyl-phenols (3a-b). The title compounds were screened for their in vitro anti-bacterial and anti-fungal activities. Results revealed that, compounds (5c), (5f), (5h) and (5j) showed excellent anti-microbial activity against a panel of microorganisms. Brine shrimp bioassay was also carried out to study their in vitro cytotoxic properties among which (5h) and (5j) displayed potent cytotoxic activity against Artemia salina. The DNA cleavage activity of some compounds was studied by agarose gel electrophoresis method. All synthesized compounds were characterized using IR, (1)H NMR, (13)C NMR, MS and elemental analysis.

Synthesis, in-vitro microbial and cytotoxic studies of new benzimidazole derivatives.

Several new classes of benzimidazole derivatives were synthesized and evaluated for in-vitro antimicrobial and cytotoxic activities. The results showed that all synthesized compounds exhibited moderate antimicrobial activity, and compounds 2, 4, and 13 displayed cytotoxic activity (as LD(50)) at the concentration 1 x 10(-3) M against Artemia salina.

Synthesis and evaluation of in vitro anti-microbial and anti-tubercular activity of 2-styryl benzimidazoles.

A new series of novel 5-(nitro/bromo)-styryl-2-benzimidazoles (1-12) has been synthesized by simple, mild and efficient synthetic protocol by attempted condensation of 5-(nitro/bromo)-o-phenylenediamine with trans-cinnamic acids in ethylene glycol. Screening for in vitro anti-tubercular activity against Mycobacterium tuberculosis H(37) Rv, anti-bacterial activity against Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae bacterial strains and anti-fungal activity against Candida albicans and Asperigillus fumigatus fungal strains were carried out. Compounds 5, 7, 8, 9, 11 showed higher anti-tubercular activity and compounds 7, 8, 10, 11, 12 have proved to be effective with MIC (microg/ml) and emerged as lead molecules showing excellent activities against a panel of microorganisms. All synthesized compounds were characterized using IR, (1)H, (13)C NMR, GC-MS and elemental analysis.

Development of 5-fluorouracil loaded poly(acrylamide-co-methylmethacrylate) novel core-shell microspheres: in vitro release studies.

Novel poly(acrylamide-methylmethacrylate) copolymeric core-shell microspheres crosslinked with N,N'-methylene bisacrylamide have been prepared by free radical emulsion polymerization using varying amounts of acrylamide (AAm), methylmethacrylate (MMA) and N,N'-methylene bisacrylamide (NNMBA). 5-Fluorouracil was loaded into these microspheres during in situ polymerization (method-I) as well as by the absorption and adsorption technique (method-II). The core-shell microspheres have been characterized by differential scanning calorimetry (DSC) and X-ray diffractometry (X-RD) to understand about the drug dispersion in microspheres. Scanning electron microscopy (SEM) was used to assess the surface morphology of particles prepared. In vitro release of 5-fluorouracil has been studied in terms of core-shell composition, amount of crosslinking agent and amount of 5-fluorouracil in the microspheres. Core-shell microspheres with different copolymer compositions have been prepared in yields ranging 80-85%. DSC and X-RD techniques indicated a uniform distribution of 5-fluorouracil particles in core-shell microspheres, whereas SEM suggested the formation of well-defined core-shell structures. The in vitro drug release indicated that particle size and release kinetics depend upon copolymer composition, amount of crosslinking agent used and amount of 5-fluorouracil present in the microspheres. Prolonged and controlled release of 5-fluorouracil was achieved when drug was loaded by method-I instead of method-II.

Distillery wastewater treatment by the membrane-based nanofiltration and reverse osmosis processes.

A hybrid nanofiltration (NF) and reverse osmosis (RO) pilot plant was used to remove the color and contaminants of the distillery spent wash. The feasibility of the membranes for treating wastewater from the distillery industry by varying the feed pressure (0-70 bar) and feed concentration was tested on the separation performance of thin-film composite NF and RO membranes. Color removal by NF and a high rejection of 99.80% total dissolved solids (TDS), 99.90% of chemical oxygen demand (COD) and 99.99% of potassium was achieved from the RO runs, by retaining a significant flux as compared to pure water flux, which shows that membranes were not affected by fouling during wastewater run. The pollutant level in permeates were below the maximum contaminant level as per the guidelines of the World Health Organization and the Central Pollution Control Board specifications for effluent discharge (less than 1,000 ppm of TDS and 500 ppm of COD).