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Aims: The study aims to synthesize bioactive hybrid pharmacophores (thiazole ring and imidazo[2,1-b]thiazole system) by incorporating them into one biological assessment molecular system., Background: A literature survey revealed that various imidazo[2,1-b]thiazoles, thiazoles, and hydrazones have powerful antimycobacterial activity., Objective: This study demonstrates the effectiveness of molecular hybridization and the scope for imidazo[2,1-b]thiazole-hydrazone-thiazoles to develop as promising antimycobacterial agents., Methods: Several imidazo[2,1-b]thiazole-hydrazine-thiazoles 5a-g, 7a,b, 9a,b, 11a,b, 13, and 15a,b were generated using a molecular hybridization strategy and assessed against Mycobacterium tuberculosis (ATCC 25618) for their in vitro antituberculous activity., Results: Derivative 7b (MIC = 0.98 μg/mL) has shown the most promising antimycobacterial activity among the series tested. Brief structure-activity relationship studies found that the thiazole of chlorophenyl or pyridine, or coumarin had a significant relation with the antimycobacterial activity., Conclusion: The promising antimycobacterial activity of compound 7b compared with the reference drug suggests that this compound may contribute as a lead compound in the search for new potential antimycobacterial agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Hybrid drug design has developed as a prime method for the development of novel anticancer therapies that can theoretically solve much of the pharmacokinetic disadvantages of traditional anticancer drugs. Thus a number of studies have indicated that thiazole-thiophene hybrids and their bis derivatives have important anticancer activity. Mammalian Rab7b protein is a member of the Rab GTPase protein family that controls the trafficking from endosomes to the TGN. Alteration in the Rab7b expression is implicated in differentiation of malignant cells, causing cancer., Methods: 1-(4-Methyl-2-(2-(1-(thiophen-2-yl) ethylidene) hydrazinyl) thiazol-5-yl) ethanone was used as building block for synthesis of novel series of 5-(1-(2-(thiazol-2-yl) hydrazono) ethyl) thiazole derivatives. The bioactivities of the synthesized compounds were evaluated with respect to their antitumor activities against MCF-7 tumor cells using MTT assay. Computer-aided docking protocol was performed to study the possible molecular interactions between the newly synthetic thiazole compounds and the active binding site of the target protein Rab7b. Moreover, the in silico prediction of adsorption, distribution, metabolism, excretion (ADME) and toxicity (T) properties of synthesized compounds were carried out using admetSAR tool., Results: The results obtained showed that derivatives 9 and 11b have promising activity (IC 50 = 14.6 ± 0.8 and 28.3 ± 1.5 µM, respectively) compared to Cisplatin (IC 50 = 13.6 ± 0.9 µM). The molecular docking analysis reveals that the synthesized compounds are predicted to be fit into the binding site of the target Rab7b. In summary, the synthetic thiazole compounds 1-17 could be used as potent inhibitors as anticancer drugs., Conclusion: Promising anticancer activity of compounds 9 and 11 compared with cisplatin reference drug suggests that these ligands may contribute as lead compounds in search of new anticancer agents to combat chemo-resistance., Competing Interests: The authors report no conflicts of interest for this work and declare that there is no conflict of interests regarding the publication of this paper., (© 2021 Gomha et al.)

Novel 2-indolinone thiazole hybrids were designed and synthesized as VEGFR-2 inhibitors based on sunitinib, an FDA-approved anticancer drug. The proposed structures of the prepared 2-indolinone thiazole hybrids were confirmed based on their spectral data and CHN analyses. The target compounds were screened in vitro for their anti-VEGFR-2 activity. All tested compounds exhibited a potent submicromolar inhibition of VEGFR-2 kinase with IC 50 values ranging from 0.067 to 0.422 μM, relative to sunitinib reference drug (IC 50  = 0.075 ± 0.002 μM). Compounds 5, 15a, 15b, 17, 19c displayed excellent VEGFR-2 inhibitory activity, comparable or nearly equipotent to sunitinib. Compound 13b stood out as the most potent against VEGFR-2 showing IC 50 value of 0.067 ± 0.002 μM, lower than that of sunitinib. In addition, the most potent derivatives were assessed for their anticancer activity against two renal cancer cell lines. Compound 13b (IC 50  = 3.9 ± 0.13 μM) was more potent than sunitinib (IC 50  = 4.93 ± 0.16 μM) against CAKI-1 cell line. Moreover, thiazole 15b displayed excellent anticancer activity against CAKI-1 cell line (IC 50  = 3.31 ± 0.11 μM), superior to that of sunitinib (IC 50  = 4.93 ± 0.16 μM). Thiazole 15b was also equipotent to sunitinib (IC 50  = 1.23 ± 0.04 μM) against A498 cell line. Besides, compound 15b revealed a safety profile much better than that of sunitinib against normal human renal cells. Furthermore, a docking study revealed a proper fitting of the most active compounds into the ATP binding site of VEGFR-2, rationalizing their potent anti-VEGFR-2 activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)