Full Paper Synthesis and Biological Evaluation of Some 2,4,5- Trisubstituted Thiazole Derivatives as Potential Antimicrobial and Anticancer Agents Mohammed S. Al-Saadi, Hassan M. Faidallah, and Sherif A. F. Rostom Department of Medicinal Chemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia We report on the synthesis and biological evaluation of two series of 2,4,5-polysubstituted thia- zoles comprising the acid hydrazide functionality and some derived pharmacophores known to contribute to various chemotherapeutic activities. All newly synthesized compounds were sub- jected 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 activ- ity against C. albicans. Potential antibacterial and antifungal activities were linked to the thiose- micarbazide function 6a – f and those substituted with both the thioureido and thiosemicarba- zide 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. albi- cans. 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 com- pounds 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. Keywords: Acid hydrazides / Antibacterial / Anticancer activity / Antifungal / Thiazoles / Received: January 26, 2008; accepted: April 4, 2008 DOI 10.1002/ardp.200800026 Introduction The past few years have witnessed an obvious reduction in the mortality caused by infectious diseases and a rise in the control of neoplastic pathologies. Nevertheless, the emergence of Gram-positive and Gram-negative pathogenic bacteria resistant to currently marketed anti- bacterial agents has reached an alarming level in many countries [1]. Moreover, there has been a rapid spread in primary and opportunistic fungal infections because of the increased number of immunocompromised patients (AIDS, cancer, and transplants). Candida albicans is one of the most common opportunistic fungi responsible for such type of infections [2]. Infections caused by these microorganisms pose a serious challenge to the medical community and highlight the importance and urgent need for new, more potent and selective non-traditional antimicrobial agents. On the other hand, chemotherapy is, at present, the only effective therapy for some types of disseminated cancers [3]. Consequently, great expecta- Correspondence: Prof. Sherif A. F. Rostom, Ph.D., Associate Professor of Medicinal Chemistry, Department of Medicinal Chemistry, Faculty of Medicine, King Abdulaziz University, P.O. Box 80205, Jeddah 21589, Saudi Arabia. E-mail: sherifrostom@yahoo.com Fax: +966 2-6400000-22327 Abbreviations: inhibition zones (IZ) i 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 424 Arch. Pharm. Chem. Life Sci. 2008, 341, 424 – 434