DESIGN, MOLECULAR MODELING AND SYNTHESIS OF NEW IMMUNOMODULATORY AGENTS FOR BIOLOGICAL STUDIES

Document Type : Original Article

Author

Department of Pharmaceutical Medicinal Chemistry & Drug Design, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt.

Abstract

Cancer is the second leading cause of death worldwide. This work is an effort to find new effective and safe anticancer agents. In accordance with thalidomide features as immunomodulator anticancer drug, we designed and synthesized ten new thalidomide analogs. The synthesized compounds were biologically evaluated for their anti-tumor activity against three human cancer cell lines namely; hepatocellular carcinoma (HepG2), prostate cancer (PC3) and breast cancer (MCF-7). Thalidomide was used as a reference drug. The obtained data showed that compound 10a is far better than thalidomide against the three cancer cell lines. It exhibited IC50 = 3.89, 4.01 and 2.91 µg/mL against the cell lines, respectively. While thalidomide exhibited IC50 values of  11.26, 14.58, and 16.87 µg/mL against the three cell lines, respectively. Moreover, compounds 7a, 6a and 8 were found to be better than thalidomide against MCF-7 cell line. As they showed IC50  values of 10.32, 12.15 and 15.32 µg/mL, respectively. Furthermore, compounds 6a, 7a, and 8 showed strong activity against the three cell lines. Results of docking studies showed that our compounds can accommodate the pocket of CRBN with binding energies too close to that of thalidomide.

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Al-Azhar Journal of Pharmaceutical Sciences
Volume 64, Issue 2 - Serial Number 2
September and October 2021
Pages 1-20

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