Design and Synthesis of Hybrid Compounds as Epigenetic Modifiers

Author(s)

Lopes, Juliana Romano ^[1] ; Prokopczyk, Igor Muccilo ^[1] ; Gerlack, Max ^[1] ; Man Chin, Chung ^[1] ; Santos, Jean Leandro Dos ^[1]

Affiliation

^[1] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, BR-14800903 Araraquara, SP - Brazil

• Document type: Journal article
• Source: PHARMACEUTICALS; v. 14, n. 12 DEC 2021.
• Web of Science Citations: 0

Abstract

Epigenetic modifiers acting through polypharmacology mechanisms are promising compounds with which to treat several infectious diseases. Histone deacetylase (HDAC) enzymes, mainly class I, and extra-terminal bromodomains (BET) are involved in viral replication and the host response. In the present study, 10 compounds were designed, assisted by molecular docking, to act against HDAC class I and bromodomain-4 (BRD4). All the compounds were synthesized and characterized by analytical methods. Enzymatic assays were performed using HDAC-1, -4, and -11 and BRD4. Compounds (2-10) inhibited both HDAC class I, mainly HDAC-1 and -2, and reduced BRD4 activity. For HDAC-1, the inhibitory effect ranged from 8 to 95%, and for HDAC-2, these values ranged from 10 to 91%. Compounds (2-10) decreased the BRD4 activity by up to 25%. The multi-target effects of these compounds show desirable properties that could help to combat viral infections by acting through epigenetic mechanisms. (AU)

• FAPESP's process: 18/11079-0 - Synthesis and antitubercular activity of new N-oxide compounds designed to treat multiresistant-tuberculosis
• Grantee: Jean Leandro dos Santos
• Support Opportunities: Regular Research Grants