Potent ACE inhibitors from 5-hydroxy indanone derivatives.

A novel triazole derivatives(±)-2-(hydroxymethyl)-7,8-dihydro-1H-indeno[5,4-b]furan-6(2H)-one (12a-j) were designed and synthesized by the reaction between racemic azide and terminal acetylenes under click chemistry reaction conditions followed by biological evaluation as angiotensin converting enzyme (ACE) inhibitors. ß-Amino alcohol derivatives of 1-indanone (15a-l) were synthesized from 5-hydroxy indanone, it was reacted with epichlorohydrin and followed by oxirane ring opening with various piperazine derivatives. Among the newly synthesized compounds 12b (IC50: 1.388024 µM), 12g (IC50: 1.220696 µM), 12j (IC50: 1.312428 µM) and 15k (IC50: 1.349671 µM) and 15l (IC50: 1.330764 µM) emerged as most active non-carboxylic acid ACE inhibitors with minimal toxicity comparable to clinical drug Lisinopril.

Design, synthesis and in vitro anti-tuberculosis activity of benzo[6,7]cyclohepta[1,2-b]pyridine-1,2,3-triazole derivatives.

A series of novel benzo[6,7]cyclohepta[1,2-b]pyridine-1,2,3-triazole hybrids (7a-j &8a-j) have been designed and synthesized in excellent yields by Huisgen's [3+2] cyclo addition reaction of 3-(azidomethyl)-2-methyl-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine (5) with various alkynes 6 in presence of copper sulphate and sodium ascorbate and their structures were confirmed by IR, 1H NMR, 13C NMR and HRMS. The newly synthesized compounds 7a-j &8a-j were evaluated for their in vitro anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC 27294). Among the compounds tested, the compounds 7i and 8g displayed most potent activity with MIC value of 1.56 µg/mL with low cytotoxicity.

Design, synthesis, and in vitro antituberculosis activity of benzo[6,7]cyclohepta[1,2-b]pyridine-1,3,4-oxadiazole derivatives.

A new antitubercular agents, benzo[6,7]cyclohepta[1,2-b]pyridine-1,3,4- oxadiazole hybrids (6a-o), have been designed and synthesized involving oxidative cyclization of hydrazones by use of di(acetoxy)iodobenzene, characterized by IR,1 H NMR,13 C NMR, and HRMS, and further confirmed by X-ray analysis. All the newly synthesized compounds 4a-o evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC27294). Among the compounds tested, the compounds 4o (MIC: 1.56 µg/ml) and 4l, 4m (MIC: 3.125 µg/ml) are promising lead analogues and have shown lower cytotoxicity.

A novel piperazine linked ß-amino alcohols bearing a benzosuberone scaffolds as anti-proliferative agents.

A new series of 1-((9-chloro-2,3-dimethyl-6,7-dihydro-5H-benzo[7]annulen-8-yl)methoxy)-3-(4-phenylpiperzin-1-yl) propan-2-ols (6a-k) have been designed, synthesized and their structures were established by spectroscopic data (FT-IR, 1H NMR, 13C NMR, HRMS) and further confirmed by X-ray analysis. The newly synthesized compounds 6a-k were evaluated for their in vitro anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MDA-MB-231 (breast), A549 (lung) and MIAPACA (pancreatic). Among the compounds tested, the compound 6e displayed most potent activity against four cancer cell lines with GI50 values ranging from 0.010 to 0.097µM. The structure and anti-proliferative activity relationship was further supported by in silico molecular docking study of the active compounds against Colchicine binding site of ß-tubulin.

A convenient synthesis and screening of benzosuberone bearing 1,2,3-triazoles against Mycobacterium tuberculosis.

A series of benzosuberone bearing 1,2,3-triazoles were rationally designed and alkyl/aryl groups appended on 1,2,3-triazole derivatives 5a-o were synthesized using click chemistry and evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC27294). Compounds 5h (MIC: 3.125µg/mL) and 5l, 5m, 5o (MIC: 6.25µg/mL) exhibited promising hits. This is the first Letter on the synthesis and in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv of benzosuberone alkyl/aryl groups appended on 1,2,3-triazole derivatives.

Three-component, one-pot synthesis of benzo[6,7]cyclohepta[1,2-b]pyridine derivatives under catalyst free conditions and evaluation of their anti-inflammatory activity.

An efficient three-component protocol is described for the synthesis of benzo[6,7]cyclohepta[1,2-b]pyridine derivatives using ß-chloroacroleins, 1,3-dicarbonyls and ammonium acetate under catalyst free conditions by using ethanol as reaction media. The mild reaction conditions, operational simplicity and high yields are the advantages of this protocol and the broad scope of this one-pot reaction makes this procedure promising for practical usages. All the final compounds were screened for anti-inflammatory activity. Among the compounds tested, the compounds 5a, 5b, 5c, 5d, 5f, and 5k exhibited significant inhibition of IL-1ß and MCP-1 secretion as a measure of anti-inflammatory activity.