title: Design and synthesis of imidazo[2,1-b]thiazole linked triazole conjugates: Microtubule-destabilizing agents.
abstract: A series of imidazo[2,1-b]thiazole linked triazole conjugates were synthesized by using Huisgen 1,3-dipolar cyclo-addition reaction (click chemistry approach) and evaluated for their antiproliferative activity against some human cancer cell lines like, HeLa (cervical), DU-145 (prostate), A549 (lung), MCF-7 (breast) and HepG2 (liver). Among them, Conjugates 4g and 4h demonstrated a significant antiproliferative effect against human lung cancer cells (A549) with IC50values of 0.92 and 0.78 μM respectively. Flow cytometric analysis revealed that these conjugates induced cell cycle arrest in G2/M phase in A549 lung cancer cells. The tubulin polymerization assay and immunofluorescence analysis showed that these conjugates effectively inhibit microtubule assembly in cell free and cell based (A549) experiment respectively. Moreover, the apoptosis inducing properties were evaluated by Hoechst staining, mitochondrial membrane potential and Annexin V-FITC assay. Further, western blot analysis was performed for proapoptotic protein Bax and antiapoptotic protein Bcl-2 and the results demonstrated that there was up regulation of Bax and down regulation of Bcl-2 suggesting that these compounds induced apoptosis in human lung cancer cells, A549.
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, 500007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, 500007, India.
authors.forename: Siddiq Pasha
authors.initials: SP
authors.lastname: Shaik
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, 500007, India.
authors.forename: V Lakshma
authors.initials: VL
authors.lastname: Nayak
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, 500007, India.
authors.forename: Faria
authors.initials: F
authors.lastname: Sultana
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, 500007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, 500007, India.
authors.forename: A V Subba
authors.initials: AVS
authors.lastname: Rao
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, 500007, India.
authors.forename: Anver Basha
authors.initials: AB
authors.lastname: Shaik
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, 500007, India.
authors.forename: Korrapati Suresh
authors.initials: KS
authors.lastname: Babu
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, 500007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, 500007, India; Chemistry Department, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia. Electronic address: ahmedkamal@iict.res.in.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kamal
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D008958:Models, Molecular; D020836:Protein Structure, Quaternary; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014404:Tubulin / Q000737:chemistry; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D013844:Thiazoles; D014404:Tubulin; D050257:Tubulin Modulators
keywords: Apoptosis; Cytotoxicity; Imidazo[2,1-b]thiazoles; Triazole conjugates; Tubulin depolymerization