Synthesis and SAR studies of novel 1,2,4-oxadiazole-sulfonamide based compounds as potential anticancer agents for colorectal cancer therapy.

Autor: Shamsi F; Medicinal Chemistry Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India; Genome Biology Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India., Hasan P; Medicinal Chemistry Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India., Queen A; Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India., Hussain A; Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Khan P; Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India., Zeya B; Genome Biology Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India., King HM; Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA., Rana S; Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA., Garrison J; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA., Alajmi MF; Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Rizvi MMA; Genome Biology Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India., Zahid M; Department of Environmental, Agricultural and Occupational Health, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA., Imtaiyaz Hassan M; Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India., Abid M; Medicinal Chemistry Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India. Electronic address: mabid@jmi.ac.in.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2020 May; Vol. 98, pp. 103754. Date of Electronic Publication: 2020 Mar 13.
DOI: 10.1016/j.bioorg.2020.103754
Abstrakt: A diverse series of 1,2,4-oxadiazoles based substituted compounds were designed, synthesized and evaluated as anticancer agents targeting carbonic anhydrase IX (CAIX). Initial structure-activity analysis suggested that the thiazole/thiophene-sulfonamide conjugates of 1,2,4-oxadiazoles exhibited potent anticancer activities with low μM potencies. Compound OX12 exhibited antiproliferative activity (IC 50  = 11.1 µM) along with appreciable inhibition potential for tumor-associated CAIX (IC 50  = 4.23 µM) isoform. Therefore, OX12 was structurally optimized and its SAR oriented derivatives (OX17-27) were synthesized and evaluated. This iteration resulted in compound OX27 with an almost two-fold increase in antiproliferative effect (IC 50  = 6.0 µM) comparable to the clinical drug doxorubicin and significantly higher potency against CAIX (IC 50  = 0.74 µM). Additionally, OX27 treatment decreases the expression of CAIX, induces apoptosis and ROS production, inhibited colony formation and migration of colon cancer cells. Our studies provide preclinical rational for the further optimization of identified OX27 as a suitable lead for the possible treatment of CRC.
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 Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: