Synthesis and Antiproliferative and Antilipolytic Activities of a Series of 1,3- and 1,4-Bis[5-(R-sulfanyl)-1,2,4-triazol-3-yl)benzenes

Abstract

A series of 1,3 and 1,4-bis[5-(R-sulfanyl)-1,2,4-triazol-3-yl)benzene derivatives were synthesized by the reac tion of isophthalic and terephthalic acid hydrazides with methyl and aryl isothiocyanates, followed by base-catalyzed cyclization and alkylation of the resulting bis-triazolethiols with alkyl bromides. The suggested obesity-colorectal cancer association initiated evaluation of the antiproliferative activity of the newly syn thesized compounds against a panel of obesity-related colorectal cells and inhibition of pancreatic lipase (PL). In vitro enzymatic, colorimetric, and cell culture bioassays were carried out with respective reference agents. Among the tested compounds, 1,3-bis{5-[(4-bromobenzyl)sulfanyl]-4-methyl-4H-1,2,4-triazol-3-yl}ben zene showed clearly promising, though unselective, cytotoxicity in HT29, HCT116, SW620, CACO2, and SW480 cancer cells with a PL-IC 50 value of 9.57±1.21 μM (<10 μM). Hence, the pharmacophores of most promising compounds can be druggable leads with a novel duality of antidiabesity-antineoplastic capacities and optimized potency and safety. Mechanistic examinations for hindrance of lipolysis catalysis and apoptogenic growth inhibition propensity may be attempted.

Preparation and Characterization of Capsaicin Encapsulated Polymeric Micelles and Studies of Synergism with Nicotinic Acids as Potential Anticancer Nanomedicines

“…For the viability reduction by combinations of NA compounds with capsaicin or nano-form capsaicin on MCF7, PC3, CACO2, A375, PANC1 and A549 cell lines was assessed with different concentrations. [ 41 42 43 44 45 46 47 ].…”

Antioxidant and antibacterial activities of 5-mercapto(substitutedthio)-4-substituted-1,2,4-triazol based on nalidixic acid: A comprehensive study on its synthesis, characterization, and In silico evaluation

“…The abundance of biological activities of 1,2,4-triazole derivatives, such as their antifungal [ 7 , 8 ], antitubercular [ 9 ], antioxidant [ 10 ], anticancer [ 11 , 12 ], anti-inflammatory [ 13 ], analgesic [ 14 ], antidiabetic [ 15 ], anticonvulsant [ 16 ], and anxiolytic activity [ 17 ], has recently piqued the interest of researchers. Triazole-based pharmacophores have supplanted the formerly common imidazole pharmacophore in systemically active azoles with regard to their antifungal activity because of lower toxicity, higher bioavailability, greater fungal cytochrome p450 selectivity, and a reduced effect on the production of human sterols [ 18 ].…”