382 ISSN 1068-1620, Russian Journal of Bioorganic Chemistry, 2020, Vol. 46, No. 3, pp. 382–392. © Pleiades Publishing, Ltd., 2020. Synthesis of Some New Pyrazoline-Based Thiazole Derivatives and Evaluation of Their Antimicrobial, Antifungal, and Anticancer Activities Safaa I. Elewa a , Eman Mansour a , Ibrahim F. Nassar b, 1 , and Amal A. I. Mekawey c a Department of Chemistry, Faculty of Women for Arts, Science and Education, Egypt, Ain Shams University, Cairo, 11566 Egypt b Faculty of Specific Education, Ain Shams University, Abassia, Cairo, 11566 Egypt c The Regional Center of Mycology and Biotechnology, Al-Azhar University, Cairo, 11651 Egypt Received May 27, 2019; revised July 3, 2019; accepted December 20, 2019 Abstract—3-(2-Thienyl)-5-aryl-1-thiocarbamoyl-2-pyrazolines were reacted with chloroacetone deriva- tives and hydrazonyl chloride derivatives in ethanol to afford the corresponding thiazolylpyrazoline deriv- atives and thiophenylpyrazolyl-5-substituted aryl-diazenylthiazole derivatives, respectively. The structures of the newly synthesized compounds were elucidated by different elemental and spectral analyses (IR, mass, 1 H and 13 C NMR). The antimicrobial and antifungal activities of the newly synthesized compounds were evaluated against four bacterial species and five fungal strains. In addition, the antitumor activities of two of the newly synthesized compounds 1-(2-(5-(4-chlorophenyl)-3-(thiophen-2-yl)-4,5-dihydropyra- zol-1-yl)-4-methyl thiazol-5-yl)ethan-1-one and 2-(5-(4-chlorophenyl)-3-(thiophen-2-yl)-4,5-dihydro- 1H-pyrazol-1-yl)-4-methyl-5-(phenyl-diazenyl)thiazole against HEPG-2, HCT-116, MCF-7, BHK, and CACO-2 were evaluated. From the obtained results, we found that these two compounds were the most potent candidates towards all gram-positive and gram-negative bacteria, as well as the fungi studied. Also, the same two compounds showed strong antitumor activities against two of the tumor cell lines (HCT-116 and CACO-2). Keywords: thiophene, thiazole, pyrazoline, antimicrobial, antifungal, anticancer activity DOI: 10.1134/S1068162020030061 INTRODUCTION The presence of pyrazole nucleus in different structures leads to diversified applications in different areas, such as technology, medicine, and agriculture. In particular, they are described as inhibitors of pro- tein glycation, antibacterial, antifungal, anti-tubercu- losis, antioxidant, and antiviral agents [1, 2]. Com- pounds including a pyrazole nucleus exhibit a wide spectrum of biological activities, such as antimicro- bial, anti-inflammatory, antidepressant, and antican- cer effects. Among the reported activities, it is import- ant to note that pyrazolines are not only useful in treatment of various cancer types, including brain, bone, mouth, esophagus, stomach, liver, bladder, pancreas, cervix, lung, breast, colon, rectum, and prostate cancers, but also some of them act as cancer chemopreventive agents [3–21]. Also, pyrazoline derivatives were reported as epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors [17], aurora kinase inhibitors [18], COX-2/B-Raf inhibitors [19], telomerase inhibitors [20], and tubulin assem- bling inhibitors [21]. On the other hand, thiazole has been recognized as a promising scaffold for the design and development for central nervous system (CNS) active agents. There are thiazole-based CNS drugs currently used as therapeutic agents for the treatment of various CNS disorders and a number of thiazole derivatives are in clinical trials [22]. Diverse modifica- tions of the thiazole ring at various positions have led to a variety of thiazole-based CNS agents as AChE and BuChE inhibitors, secretase inhibitors, mono- amine oxidase (MAO) inhibitors, neuronal nitric oxide synthase inhibitors, Ach receptor ligands, ade- nosine receptor ligands, dopamine receptor ligands, serotonin receptor ligands, glutamate receptor ligands, γ-aminobutyric acid receptor ligands, opioid receptor ligands, neuroprotective, and anticonvulsant agents [22–25]. Acotiamide has been reported to be a prom- 1 Corresponding author: e-mail: Dr.Ibrahim.Nassar@ sedu.asu.edu.eg.