Synthesis and Biological Evaluation of Some 2,4,5‐Trisubstituted Thiazole Derivatives as Potential Antimicrobial and Anticancer Agents

Abstract

We report on the synthesis and biological evaluation of two series of 2,4,5-polysubstituted thiazoles comprising the acid hydrazide functionality and some derived pharmacophores known to contribute to various chemotherapeutic activities. All newly synthesized compounds were subjected to in-vitro antibacterial and antifungal screening. Of the compounds tested, 13 derivatives displayed inhibitory effect on the growth of three Gram-positive strains while they lack activity against Gram-negative bacteria. Moreover, four compounds were able to exert antifungal activity against C. albicans. Potential antibacterial and antifungal activities were linked to the thiosemicarbazide function 6a-f and those substituted with both the thioureido and thiosemicarbazide moieties 12a-f. Compounds 6f and 12f (R = 4-F-C(6)H(4)) could be considered as the most active members in this investigation with a broad spectrum of antibacterial activity against three types of Gram-positive bacteria, together with an appreciable antifungal activity against C. albicans. Compounds 6d, 6f, and 12f were twice as active as ampicillin against B. subtilis. The best antifungal activity was shown by compound 6d 50% less active than clotrimazole. 17 compounds were selected and tested for their preliminary in-vitro anticancer activity according to the current one-dose protocol of the NCI. Three cell lines, non-small cell lung cancer Hop-92, ovarian cancer IGROV1, and melanoma SK-MEL-2, exhibited some sensitivity against most of the tested compounds. Compound 12f proved to be the most active anticancer member with a broad spectrum of activity against most of the tested subpanel tumor cell lines. Consequently, 12f was carried over to be tested in the five-dose assay.

Synthesis and anticancer and cytotoxic effects of novel 1,4-phenylene-bis-N-thiocarbamoylpyrazole and 1,4-phenylene-bis-pyrazolylthiazole derivatives

“…Moreover, thiazole derivatives are useful compounds for synthesis of biologically active agents like antimicrobial, 12 anticancer, 13,14 analgesic, and anti-inflammatory agents. 15 A large number of thiazole derivatives have potent anticancer activity and show selective activity against HeLa cancer cells.…”

Design, Synthesis and Docking Studies of Novel 1, 2, 3-Triazolyl Phenylthiazole Analogs as Potent Anti-HIV-1 NNRT Inhibitors

“…The 2-amino-1,3-thiazoles are biologically important compounds with a wide range of medicinal and biological applications including antibacterial, antifungal, anti-HIV, anti-hypertension, antiinflammatory, anticancer, anticonvulsant, and antidepressant [1][2][3][4][5][6]. Some 2-amino-1,3-thiazole derivatives have been reported as ligands of thrombopoietin [7,8], neuropeptide Y5 [9] and adenosine receptors [10,11] and as inhibitors of several physiological important enzymes like cyclindependant kinase [12], poly (ADP-Ribose) polymerase [13], urokinase [14] etc.…”

Synthesis, Characterization and Biological Evaluation of Some Benzothiazole Derivatives as Potential Antimicrobial Agent.

“…They are also useful as anti-allergic 13 , anti-inflammatory 14 and anthelmintic 15 agents and as appetite depressants 16 , intermediates for dyes 17 , plant protectants 18 , histamine H2antagonists 19 and photographic sensitizers 20 . On the other hand, careful literature survey revealed that thiazole, thiophene and pyrazole ring systems have occupied a unique position in the design and synthesis of novel biological active agents with remarkable analgesic and antiinflammatory activities [21][22][23] , in addition to their well documented potential antimicrobial activities [24][25][26][27] . Morever, thiazoles have found application in drug development for the treatment of hypertension 28 , schizophrenia 29 , HIV infections 30 , and as new inhibitors of bacterial DNA gyrase B 31 .…”