Green Synthesis of Some Novel Bis-Heterocycles of Expected Biological Activity

Abstract

Bis-thiadiazole derivatives were synthesized in high yield via the reaction of 2,2'-terephthaloyl bis(N-phenylhydrazinecarbothioamide) with a variety of hydrazonoyl chlorides in ethanol containing catalytic amounts of TEA. The molecular docking of the most active derivative 15b against the human dopamine D3 receptor was performed by the Molecular Operating Environment (MOE 2014. 0901) program. Moreover, a novel series of bis(1,3,4-thiadiazole) derivatives were synthesized as a sole product in one step methodology by reaction of bis-hydrazonoyl chloride with many of hydrazinecarbodithioate derivatives 214, 218a-e, 223a-e and 228. Compounds 234c, 236d, 232b and 234d were the most active (IC50 values of 0.37 ± 0.15, 0.93 ± 0.32, 1.03 ± 0.45 and 3.52 ± 0.43 µg/mL, respectively) against human breast carcinoma cell line (MCF-7) and compounds 234c, 236d, 232b and 234d were the most active (IC50 value of 0.38 ± 0.12, 0.88 ± 0.46, 2.15 ± 0.16 and 2.47 ± 0.44 µg/mL, respectively) against the human hepatocellular carcinoma cell line (HepG-2). To reach what we want from that study, we have aminohydrazide Cross-Linked chitosan (CLCS) and its MWCNTs (CLCS/MWCNTs) composite as ecofriendly biocatalysts for synthesis of some novel bis-thiazoles and bis-thiadiazoles. CLCS/MWCNTs composite was characterized by a greater surface area and a higher thermal stability than CLCS. Thus, CLCS/MWCNTs composite was served as a powerful ecofriendly basic biocatalyst under ultrasonic irradiation in the synthesis of three novel series of 1,2-bis(2-(4-methyl-5-(aryldiazenyl)thiazol-2-yl)hydrazono)-1,2-diphenylethane 241a-g, 2,2'-(2,2'-(1,2-diphenylethane-1,2-diylidene)bis-(hydrazin-1-yl-2-ylidene))-