Thiophene-Linked 1,2,4-Triazoles: Synthesis, Structural Insights and Antimicrobial and Chemotherapeutic Profiles.

The reaction of thiophene-2-carbohydrazide or 5-bromothiophene-2-carbohydrazide with various haloaryl isothiocyanates and subsequent cyclization by heating in aqueous sodium hydroxide yielded the corresponding 4-haloaryl-5-(thiophen-2-yl or 5-bromothiophen-2-yl)-2,4-dihydro-3-1,2,4-triazole-3-thione -. The triazole derivatives and were reacted with different secondary amines and formaldehyde solution to yield the corresponding 2-aminomethyl-4-haloaryl-2,4-dihydro-3-1,2,4-triazole-3-thiones -, -, , , and in good yields. The in vitro antimicrobial activity of compounds -, -, -, , , and was evaluated against a panel of standard pathogenic bacterial and fungal strains. Compounds , , , , -, -, , , and showed marked activity, particularly against the tested Gram-positive bacteria and the Gram-negative bacteria , and all the tested compounds were almost inactive against all the tested fungal strains. In addition, compounds , -, - and exhibited potent anti-proliferative activity, particularly against HepG-2 and MCF-7 cancer cell lines (IC < 25 μM). A detailed structural insight study based on the single crystals of compounds , , , and is also reported. Molecular docking studies of the highly active antibacterial compounds , , , and showed a high affinity for DNA gyrase. Meanwhile, the potent anti-proliferative activity of compounds , and may be attributed to their high affinity for cyclin-dependent kinase 2 (CDK2).