title: A novel triazole derivative of betulinic acid induces extrinsic and intrinsic apoptosis in human leukemia HL-60 cells.
abstract: In an attempt to arrive at more potent cytotoxic agent than the bioactive natural product betulinic acid, influence of small structural modifications of its 1, 2, 3 triazole derivatives tethered at C-28 and both C3, C-28 using click chemistry approach has been studied. The chemically characterized triazoles have been screened for in vitro cytotoxicity against four human cancer cell lines HL-60, MiaPaCa-2, PC-3 and A549 which has allowed to identify triazole derivative 28{1N (4-fluoro phenyl)-1H-1, 2, 3-triazol-4-yl} methyloxy betulinic ester having better potency profile than the parent compound with IC50 values in the range of 5-7 μM. It caused disruption of mitochondrial membrane potential, rendered Bcl-2 cleavage, Bax translocation and decrease Bcl-2/Bax ratio. These events are accompanied by activation of caspases -9, -3, which cleave the PARP-1. It also induces caspase-8, which is involved in extrinsic apoptotic pathway. Therefore, it induces apoptosis through both intrinsic and extrinsic pathways in human leukemia HL-60 cells.
authors.affiliation: Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Imran
authors.initials: I
authors.lastname: Khan
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Guru
authors.affiliation: Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IIIM Campus, Jammu, India.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Rath
authors.affiliation: Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Chinthakindi
authors.affiliation: Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Buddh
authors.initials: B
authors.lastname: Singh
authors.affiliation: Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Surrinder
authors.initials: S
authors.lastname: Koul
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India. Electronic address: sbhushan@iiim.ac.in.
authors.forename: Shashi
authors.initials: S
authors.lastname: Bhushan
authors.affiliation: Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IIIM Campus, Jammu, India. Electronic address: plsangwan@iiim.ac.in.
authors.forename: Payare L
authors.initials: PL
authors.lastname: Sangwan
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D015394:Molecular Structure; D053978:Pentacyclic Triterpenes; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000094062:Betulinic Acid
chemical_list: D000970:Antineoplastic Agents; D053978:Pentacyclic Triterpenes; D014230:Triazoles; D014315:Triterpenes; D000094062:Betulinic Acid
keywords: Apoptosis; Betulinic acid; Click chemistry; Human leukemia; Triazole derivative