Molecular docking, synthesis, characteristics and preliminary cytotoxic study of new coumarin-sulfonamide derivatives as histone deacetylase inhibitors.

OBJECTIVE: Aim: To evaluate the cytotoxic activity of newly synthesized a series of novel HDAC inhibitors comprising sulfonamide as zinc binding group and Coumarin as cap groups. PATIENTS AND METHODS: Materials and Methods: The utilization of sulfonamide as zinc binding group and Coumarin as cap groups known to possess antitumor activity in the designed of new histone deacetylase inhibitors and using the docking and MTT assay to evaluate the compounds. RESULTS: Results: Four compounds have been synthesized and characterized successfully by ART-FTIR, NMR and ESI-Ms. The synthesized compound assessed for their cytotoxic activity against hepatoblastoma HepG2 (IC50, I=0.094, II=0.040, III=0.032, IV=0.046, SAHA=0.141) and human colon adenocarcinoma MCF-7 (IC50, I=0.135, II=0.050, III= 0.065, IV=0.059, SAHA=0.107). The binding mode to the active site of [HDAC6] were determined by docking study which give results that they might be good inhibitors for [HDAC6]. CONCLUSION: Conclusions: The synthesized compounds (I, II, III and IV) showed a comparable cytotoxic result with FDA approved drug (SAHA) toward HepG2 and MCF-7 cancer cell lines and their docking analysis provided a preliminary indication that they are viable [HDAC6] candidates.

Design, synthesis, insilco study and biological evaluation of new isatin-sulfonamide derivatives by using mono amide linker as possible as histone deacetylase inhibitors.

OBJECTIVE: Aim: To evaluate the cytotoxic activity of newly synthesized a series of novel HDAC inhibitors comprising sulfonamide as zinc binding group and Isatin derivatives as cap group joined by mono amide linker as required to act as HDAC inhibitors. PATIENTS AND METHODS: Materials and Methods: The utilization of sulfonamide as zinc binding group joined by N-alkylation reaction with ethyl-bromo hexanoate as linker group that joined by amide reaction with Isatin derivatives as cap groups which known to possess antitumor activity in the designed of new histone deacetylase inhibitors and using the docking and MTT assay to evaluate the compounds. RESULTS: Results: Four compounds have been synthesized and characterized successfully by ART-FTIR, NMR and ESI-Ms. the compounds were synthesized and characterized by successfully by ART-FTIR, NMR and ESI- Ms. Assessed for their cytotoxic activity against human colon adenocarcinoma MCF-7 (IC50, I=105.15, II=60.00, III=54.11, IV=56.57, vorinostat=28.41) and hepatoblastoma HepG2 (IC50, I=63.91, II=135.18, III=118.85, IV=51.46, vorinostat=37.50). Most of them exhibited potent HDAC inhibitory activity and significant cytotoxicity. CONCLUSION: Conclusions: The synthesized compounds (I, II, III and IV) showed cytotoxicity toward MCF-7 and HepG2 cancer cell lines and their docking analysis provided a preliminary indication that they are viable [HDAC6] candidates.