title: Design, synthesis and biological evaluation of β-boswellic acid based HDAC inhibitors as inducers of cancer cell death.
abstract: The synthesis and bio-evaluation of naturally occurring boswellic acids (BAs) as an alternate CAP for the design of new HDAC inhibitors is described. All the compounds were screened against a panel of human cancer cell lines to identify leads, which were subsequently examined for their potential to inhibit HDACs. The identified lead compound showed IC50 value of 6μm for HDACs, found to induce G1 cell cycle arrest at significantly low concentration (1μM) and caused significant loss in mitochondrial membrane potential at 5 and 10μM. Furthermore, specific interactions of the lead molecule inside the catalytic domain were also studied through in silico molecular modeling.
authors.affiliation: Natural Product Microbes, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi 180001, J&K, India.
authors.forename: Simmi
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi 180001, J&K, India.
authors.forename: Mudassier
authors.initials: M
authors.lastname: Ahmad
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi 180001, J&K, India.
authors.forename: Javeed Ahmad
authors.initials: JA
authors.lastname: Bhat
authors.affiliation: Natural Product Microbes, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi 180001, J&K, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi 180001, J&K, India.
authors.forename: Arvind
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Natural Product Microbes, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi 180001, J&K, India.
authors.forename: Manjeet
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Department of Biochemistry, University of Kashmir, Srinagar, India.
authors.forename: Mohmmad Afzal
authors.initials: MA
authors.lastname: Zargar
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi 180001, J&K, India. Electronic address: ahdar@iiim.ac.in.
authors.forename: Abid
authors.initials: A
authors.lastname: Hamid
authors.affiliation: Natural Product Microbes, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi 180001, J&K, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi 180001, J&K, India. Electronic address: bashah@iiim.ac.in.
authors.forename: Bhahwal Ali
authors.initials: BA
authors.lastname: Shah
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D018922:HL-60 Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D014315:Triterpenes; C054625:boswellic acid; D006655:Histone Deacetylases
keywords: Anti-cancer; HDAC; Hydroxamic acid; β-Boswellic acid