title: 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.
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.
authors.affiliation: Department of Chemistry, School of Science & Humanities, Karunya University, Coimbatore 641 114, India. Electronic address: ravichandru55@gmail.com.
authors.forename: P
authors.initials: P
authors.lastname: Ravichandiran
authors.affiliation: Department of Nanosciences & Technology, School of Nanosciences & Technology, Karunya University, Coimbatore 641 114, India.
authors.forename: A
authors.initials: A
authors.lastname: Jegan
authors.affiliation: Department of Bioinformatics, School of Biotechnology and Health Sciences, Karunya University, Coimbatore 641 114, India.
authors.forename: D
authors.initials: D
authors.lastname: Premnath
authors.affiliation: Department of Animal Science, Bharathidasan University, Tiruchirappalli 620 024, India.
authors.forename: V S
authors.initials: VS
authors.lastname: Periasamy
authors.affiliation: Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625 021, India.
authors.forename: S
authors.initials: S
authors.lastname: Muthusubramanian
authors.affiliation: Department of Chemistry, School of Science & Humanities, Karunya University, Coimbatore 641 114, India. Electronic address: kumar2359@yahoo.com.
authors.forename: S
authors.initials: S
authors.lastname: Vasanthkumar
mesh_terms: D001665:Binding Sites; D002227:Carbazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D009285:Naphthoquinones / Q000737:chemistry; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013450:Sulfones / Q000737:chemistry*
chemical_list: D002227:Carbazoles; D056572:Histone Deacetylase Inhibitors; D009285:Naphthoquinones; D012097:Repressor Proteins; D013450:Sulfones; C409470:HDAC8 protein, human; D006655:Histone Deacetylases; C035342:1,4-naphthoquinone
keywords: 1,4-Naphthoquinone; Acid chlorides; Carbazole; Cervical cancer; Molecular docking; Sulfone