title: β-Ionone derived apoptosis inducing endoperoxides; Discovery of potent leads for anticancer agents.
abstract: A series of endoperoxides (3a-j) were synthesized and evaluated for cytotoxic activity against four human cancer cell lines by using SRB dye assay. All the compounds displayed moderate to high cytotoxic effect against almost all investigational cancer cells. Particularly, compounds bearing electron withdrawing groups such as nitro substituted compound 3j (IC50 = 0.001 μM) and fluoro substituted compound 3i (IC50 = 0.003 μM) showed comparatively more cytotoxic potential than standard drugs against lung cancer cell line (A549). All synthesized endoperoxides (3a-j) were further evaluated for their apoptotic potential through various parameters such as flow-cytometric analysis of nuclear DNA, flow-cytometric determination of mitochondrial membrane potential (ΔΨm), spectrofluorimetric estimation of intracellular ROS level and caspase-3 & 9 assays in treated lung cancer cells (A549); results reveal that endoperoxides induce apoptosis in cancer cells via mitochondrial pathway.
authors.affiliation: Bio-Organic and Photochemistry Laboratory, Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143 005, Punjab, India.
authors.forename: Vishal
authors.initials: V
authors.lastname: Sharma
authors.affiliation: Department of Botanical and Environment Sciences, Guru Nanak Dev University, Amritsar 143 005, Punjab, India.
authors.forename: Ashun
authors.initials: A
authors.lastname: Chaudhry
authors.affiliation: Indian Institute of Integrative Medicine, Cancer Pharmacology Division, Jammu 180 001, J & K, India.
authors.forename: Gousia
authors.initials: G
authors.lastname: Chashoo
authors.affiliation: Department of Botanical and Environment Sciences, Guru Nanak Dev University, Amritsar 143 005, Punjab, India.
authors.forename: Rohit
authors.initials: R
authors.lastname: Arora
authors.affiliation: Department of Botanical and Environment Sciences, Guru Nanak Dev University, Amritsar 143 005, Punjab, India.
authors.forename: Saroj
authors.initials: S
authors.lastname: Arora
authors.affiliation: Indian Institute of Integrative Medicine, Cancer Pharmacology Division, Jammu 180 001, J & K, India.
authors.forename: Ajit K
authors.initials: AK
authors.lastname: Saxena
authors.affiliation: Bio-Organic and Photochemistry Laboratory, Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143 005, Punjab, India. Electronic address: mpsishar@yahoo.com.
authors.forename: Mohan Paul S
authors.initials: MP
authors.lastname: Ishar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D016466:CHO Cells; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D045792:Norisoprenoids / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D010545:Peroxides / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D045792:Norisoprenoids; D010545:Peroxides; D017382:Reactive Oxygen Species; D004247:DNA; C008157:beta-ionone; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; D053453:Caspase 9
keywords: Anticancer activity; Apoptosis; Cytotoxic activity; Endoperoxides