Identification of Novel 4-Oxo-4H-chromen-Hydroxamic Acid Derivative Targeting Selected HDAC Isoforms | ||||
| Archives of Pharmaceutical Sciences Ain Shams University | ||||
| Volume 7, Issue 2, December 2023, Page 286-302 PDF (1.08 MB) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/aps.2023.226661.1128 | ||||
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| Authors | ||||
Rosaline Ashraf  1; Mai Adel2; Rabah A. T. Serya3; Khaled A. M. Abouzid4
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| 1Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, African union organization street Abbassia, Cairo 11566, Egypt | ||||
| 2Pharmaceutical chemistry department, Faculty of Pharmacy, Ain Shams university, Cairo, Egypt | ||||
| 3Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt | ||||
| 4Professor of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt. Former Dean Faculty of Pharmacy, Sadat University in Egypt, | ||||
| Abstract | ||||
| Histone deacetylase inhibitors (HDACIs) represent a well-known class of compounds that exhibit potential therapeutic efficacy in a variety of diseases, particularly cancer and neurodegenerative disorders. This article discusses the development of compound 6 as a new HDAC inhibitor. It was designed based on the structure activity relationship (SAR) of the previously reported HDAC inhibitors and the molecular modeling studies. Compound 6 was synthesized, and its structure was verified using different spectroscopic methods. It was biologically evaluated to assess its inhibitory activity against different HDAC isoforms, including HDAC1, 6, and 8. The results showed moderate inhibition against HDAC 1 and HDAC 8 over HDAC 6. It was also evaluated for its antineoplastic activity against the NCI 60 cancer cell line panel. The results revealed inhibitory activity against both the UO-31 renal cancer cell line and the BT-549 breast cancer cell line. Moreover, the Molecular modeling studies revealed favorable binding affinity for the HDAC8 active site. These results suggest that compound 6 can be considered as a promising candidate for the development of new selective class I HDACIs in the future. | ||||
| Keywords | ||||
| HDAC; Design; Synthesis; Molecular Modeling; Hydroxamic acid; Benzopyranone | ||||
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