Access to Biologically Active Heterocyclic Systems from Carbonyl Compounds

Abstract

A novel series of tetrahydroquinolines containing acetohydrazide, oxopyrazole, oxothioxodihydropyrazole and thioxotriazole have been synthesized. A series of triazolo[4,3-a]quinoline, triazino[4,3-a]quinoline, thiadiaze- pino[5,6-b]quinoline and pyrazolquinoline have been synthesized from reaction of 2-hydrazinyltetrahydro-quinoline-3-carbonitrile with formamide, formic acid, ethyl chloroacetate, carbon disulphide in alcoholic solution of potassium hydroxide, acetyl acetone and/ or ethyl cyanoacetate respectively. Antileishmanial, antibacterial, antifungal, antitumor and cytotoxicity activities of synthesized compounds were evaluated in vitro. Antileishmanial activity of the most synthesized compounds showed tremendous activity toward L. major leishmania. Most of the synthesized tetrahydroquinolines showed antibacterial activity against five bacterial strains (S. Aureus, B. Subtilis, M. Luteus, E. aerogenase and E. coli). On the other hand, the antifungal activities of compounds under investigation have significant activities towards four fungal strains (C. Albicans, M. Canis, F. Solani and C. Glabrata). Most of the test compounds exhibited significant level of tumor inhibition. Compounds 12 and 14 showed 100 % tumor inhibition that is comparable to standard drug Vincristine (100 % tumor inhibition). Tetrahydroquinolines under investigation showed cytotoxicity with LD50 values in the range 0.56-3.01 µg/ml compared to standard drug MS-222 with LD50 value of 4.30 µg/ml. The presence of a pyazole ring markedly improved the activity profiles of tetrahydroquinolines. All newly synthesized compounds were characterized by IR, 1H-NMR, and MS.