title: Novel benzothiazine-piperazine derivatives by peptide-coupling as potential anti-proliferative agents.
abstract: In an attempt to develop potential and selective anti-proliferative agents, a series of novel benzothiazine-piperazine derivatives 8a-i and 10a-g were synthesized by coupling of 2H-1,4-benzothiazin-3(4H)-one with various amines 7a-i and 9a-g in excellent yields and evaluated for their in vitro anti-proliferative activity against four cancer cell lines, HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). In vitro inhibitory activity indicated that compounds 8a, 8d, 8g, 10a, 10b, 10e, 10f were found to be good anti-proliferative agents. Among them the derivatives 8g, 10e and 10f were found to be the most active members exhibiting remarkable growth inhibitory activity. Molecular docking was undertaken to investigate the probable binding mode and key active site interactions in HDAC8 and EHMT2 proteins. The docking results are complementary to the experimental results.
authors.affiliation: Organic Chemistry Division-II (CPC), CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: Ramineni
authors.initials: R
authors.lastname: Venkatesh
authors.affiliation: Organic Chemistry Division-II (CPC), CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: Suresh
authors.initials: S
authors.lastname: Kasaboina
authors.affiliation: Organic Chemistry Division-II (CPC), CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: Deepthi
authors.initials: D
authors.lastname: Bidayat
authors.affiliation: Organic Chemistry Division-II (CPC), CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: U
authors.initials: U
authors.lastname: Nikhil Kumar
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: Nishant
authors.initials: N
authors.lastname: Jain
authors.affiliation: Medicinal Chemistry Division, S. N. V. Pharmacy Maha Vidyalay, Tarnaka, Hyderabad 500017, India.
authors.forename: Saritha Jostna
authors.initials: SJ
authors.lastname: Tangeda
authors.affiliation: Organic Chemistry Division-II (CPC), CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: Rajashaker
authors.initials: R
authors.lastname: Bantu
authors.affiliation: Centre for Molecular Modeling, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: Sridhara
authors.initials: S
authors.lastname: Janardhan
authors.affiliation: Organic Chemistry Division-II (CPC), CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India. Electronic address: lnagarapuiict@yahoo.com.
authors.forename: Lingaiah
authors.initials: L
authors.lastname: Nagarapu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D010455:Peptides; D010879:Piperazines; D013843:Thiazines; D000077489:Piperazine
keywords: Anti-proliferative activity; Benzothiazine-piperazine; EHMT2; HDAC8; Molecular docking; Peptide-coupling