Synthesis, molecular docking and cytotoxicity evaluation of novel 2-(4-amino-benzosulfonyl)-5H-benzo[b]carbazole-6,11-dione derivatives as histone deacetylase (HDAC8) inhibitors

P Ravichandiran; A Jegan; D Premnath; V S Periasamy; S Muthusubramanian; S Vasanthkumar

doi:10.1016/j.bioorg.2014.01.002

Synthesis, molecular docking and cytotoxicity evaluation of novel 2-(4-amino-benzosulfonyl)-5H-benzo[b]carbazole-6,11-dione derivatives as histone deacetylase (HDAC8) inhibitors

Bioorg Chem. 2014 Apr:53:24-36. doi: 10.1016/j.bioorg.2014.01.002. Epub 2014 Feb 3.

Authors

P Ravichandiran¹, A Jegan², D Premnath³, V S Periasamy⁴, S Muthusubramanian⁵, S Vasanthkumar⁶

Affiliations

¹ Department of Chemistry, School of Science & Humanities, Karunya University, Coimbatore 641 114, India. Electronic address: ravichandru55@gmail.com.
² Department of Nanosciences & Technology, School of Nanosciences & Technology, Karunya University, Coimbatore 641 114, India.
³ Department of Bioinformatics, School of Biotechnology and Health Sciences, Karunya University, Coimbatore 641 114, India.
⁴ Department of Animal Science, Bharathidasan University, Tiruchirappalli 620 024, India.
⁵ Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625 021, India.
⁶ Department of Chemistry, School of Science & Humanities, Karunya University, Coimbatore 641 114, India. Electronic address: kumar2359@yahoo.com.

PMID: 24561820
DOI: 10.1016/j.bioorg.2014.01.002

Abstract

A new series of 2-(4-aminobenzosulfonyl)-5H-benzo[b]carbazole-6,11-dione derivatives, which has not been reported yet, has been synthesized from 1,4-naphthoquinone and 4-aminophenylsulfone involving an Michael addition, benzoylation and Pd catalyzed coupling. This set of compounds has been evaluated for in vitro cytotoxicity specifically against human cervical cancer cell line (SiHa) and most of the synthesized compounds exhibited good cytotoxic activity. Molecular docking of all the synthesized compounds was studied; among fourteen molecules docked compound 3 was the one with the best glide and E model score of -9.06 and -73.41, respectively which is close to the glide score of SAHA (standard). In all docked molecules, the compound 7a exhibits least glide and E model score of -2.97 and -71.02 respectively.

Keywords: 1,4-Naphthoquinone; Acid chlorides; Carbazole; Cervical cancer; Molecular docking; Sulfone.

MeSH terms

Binding Sites
Carbazoles / chemical synthesis
Carbazoles / chemistry*
Carbazoles / toxicity
Catalytic Domain
Cell Line, Tumor
Cell Survival / drug effects
Histone Deacetylase Inhibitors / chemical synthesis*
Histone Deacetylase Inhibitors / chemistry
Histone Deacetylase Inhibitors / toxicity
Histone Deacetylases / metabolism
Humans
Molecular Docking Simulation
Naphthoquinones / chemistry
Repressor Proteins / antagonists & inhibitors*
Repressor Proteins / metabolism
Sulfones / chemistry*

Substances

Carbazoles
Histone Deacetylase Inhibitors
Naphthoquinones
Repressor Proteins
Sulfones
HDAC8 protein, human
Histone Deacetylases
1,4-naphthoquinone