Synthesis and biological evaluation of imidazo[2,1-b]thiazole-benzimidazole conjugates as microtubule-targeting agents |
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| Institution: | 1. Medicinal Chemistry and Biotechnology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500007, India;2. Academy of Scientific and Innovative Research, New Delhi 110 025, India;3. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India;4. School of Pharmaceutical Education and Research(SPER), Jamia Hamdard, New Delhi 110062, India;1. Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences & Pharmaceutical Industries, Future University in Egypt, 12311 Cairo, Egypt;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt;3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Nahda University, 62511 Benisuef, Egypt;4. Department of Pharmacology and Biochemistry, Faculty of Pharmaceutical Sciences & Pharmaceutical Industries, Future University in Egypt, 12311 Cairo, Egypt;5. Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt;1. Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences & Pharmaceutical Industries, Future University in Egypt, Cairo 11835, Egypt;2. Department of Pharmacology and Biochemistry, Faculty of Pharmaceutical Sciences & Pharmaceutical Industries, Future University in Egypt, Cairo 11835, Egypt;3. Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA;4. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt;5. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Heliopolis University for Sustainable Development, Cairo 11777, Egypt;6. Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.;1. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Sichuan 610041, China;2. West China School of Pharmacy, Sichuan University, Sichuan 610041, China;3. Department of Clinical Medicine, School of Medicine, Nankai University, Tianjin, China |
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| Abstract: | A series of imidazo2,1-b]thiazole-benzimidazole conjugates were synthesized and evaluated for their antiproliferative activity against four human cancer cell lines i.e.; HeLa (cervical), A549 (lung), MCF-7 (breast) and DU-145 (prostate) along with normal HEK-293 cell line. Amongst them, conjugate 6d displayed significant cytotoxicity against human lung cancer cell line, A549 with IC50 value 1.08 µM. Further, cell cycle analysis revealed that this compound arrested the cell cycle at G2/M phase in A549 cells. Furthermore, the tubulin polymerization assay results suggest that this conjugate (6d) exhibits significant inhibitory effect on the tubulin assembly with an IC50 value of 1.68 µM. Moreover, the apoptotic inducing properties of compound 6d was confirmed by Hoechst staining, measurement of mitochondrial membrane potential (ΔΨm) and annexin V-FITC assay. Further, molecular docking studies revealed that compound 6d occupied the colchicine binding site. |
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| Keywords: | Benzimidazole Cytotoxicity Cell cycle Apoptosis |
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