title: Synthesis and evaluation of 3-salicyloylpyridine derivatives as cytotoxic mitochondrial apoptosis inducers.
abstract: A series of novel 3-salicyloylpyridines (4a-h) were synthesized with good yield by modified Knoevenagel-Stobbel method; o-allylation with allyl bromide lead to formation of compounds (5a-h). The synthesized compounds were characterized by spectroscopic techniques and evaluated for cytotoxic activity against human cancer cell lines. Compounds bearing hydroxyl group displayed high cytotoxicity (4a-h) as compared to o-allylated molecules (5a-h). The most active compound 4b was selected for further investigation to look for mechanism of cell death in prostate cancer (PC-3) cells. The apoptotic bodies induced by 4b in PC-3 cells were scanned by confocal microscopy and confirmed by scanning electron microscopy (SEM). Further results obtained from spectrofluorimetric determination of mitochondrial membrane potential (ΔΨm) and intracellular reactive oxygen species (ROS) in treated PC-3 cells revealed that mitochondria dependent apoptosis was involved in the cell death.
authors.affiliation: Bio-Organic and Photochemistry Laboratory, Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, Punjab, India.
authors.forename: Alisha
authors.initials: A
authors.lastname: Sood
authors.affiliation: Bio-Organic and Photochemistry Laboratory, Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, Punjab, India.
authors.forename: Vishal
authors.initials: V
authors.lastname: Sharma
authors.affiliation: Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar 143005, Punjab, India.
authors.forename: Ashun
authors.initials: A
authors.lastname: Chaudhry
authors.affiliation: Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar 143005, Punjab, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar 143005, Punjab, India.
authors.forename: Saroj
authors.initials: S
authors.lastname: Arora
authors.affiliation: Post-Graduate Department of Physics, University of Jammu, Jammu Tawi, 180 006, India.
authors.lastname: Rajnikant
authors.affiliation: Post-Graduate Department of Physics, University of Jammu, Jammu Tawi, 180 006, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Bio-Organic and Photochemistry Laboratory, Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, Punjab, India. Electronic address: mpsishar@yahoo.com.
authors.forename: Mohan Paul S
authors.initials: MPS
authors.lastname: Ishar
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008958:Models, Molecular; D015394:Molecular Structure; D010636:Phenols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C000596310:3-(2'-hydroxy-5'-methylbenzoyl)pyridine; D000970:Antineoplastic Agents; D010636:Phenols; D011725:Pyridines; D017382:Reactive Oxygen Species
keywords: 3-Formylchromone; 3-Salicyloylpyridines; Apoptosis; Cytotoxic activity