title: An investigation of in vitro cytotoxicity and apoptotic potential of aromatic diselenides.
abstract: A target synthesis of a library of symmetric aromatic diselenides was attempted with the aim of generating anticancer lead compounds. Out of thirteen screened molecules (1-13) against a panel of human cancer cell lines, compound 8 exhibited highest cell growth inhibition in Human leukemia HL-60 cells with IC50 value of 8 μM. Compound 8 had a good pro-apoptotic potential as evidenced from several apoptotic protocols like DNA cell cycle analysis and monitoring of apoptotic bodies formation using phase contrast and nuclear microscopy with Hoechst 33,258. Also, 8 significantly inhibits S phase of the cell cycle and eventually trigger apoptosis in HL-60 cells through mitochondrial dependent pathway substantiated by the loss of mitochondrial potential. A theoretical investigation of DNA binding ability of 8 showed that it selectively bind to minor groove of DNA, where it is stabilized by hydrogen bonding and hydrophobic interactions.
authors: Department of Chemistry, University of Kashmir, Hazratbal, Srinagar 190006, J&K, India. Electronic address: masoodku2@gmail.com.
authors: Masood Ahmad
authors: MA
authors: Rizvi
authors: Division of Cancer Pharmacology, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
authors: Santosh
authors: S
authors: Guru
authors: Department of Chemistry, University of Kashmir, Hazratbal, Srinagar 190006, J&K, India.
authors: Tahira
authors: T
authors: Naqvi
authors: Natural Product Chemistry Division, CSIR-Indian Institute of Integrative Medicine (IIIM), Canal Road, Jammu Tawi 180001, India.
authors: Manjeet
authors: M
authors: Kumar
authors: Institute of Bio-Informatics and Biotechnology, University of Pune, Ganeshkhind Road, Pune 411007, India.
authors: Navanath
authors: N
authors: Kumbhar
authors: Department of Chemistry, University of Kashmir, Hazratbal, Srinagar 190006, J&K, India.
authors: Showkat
authors: S
authors: Akhoon
authors: Department of Chemistry, University of Kashmir, Hazratbal, Srinagar 190006, J&K, India.
authors: Shazia
authors: S
authors: Banday
authors: Division of Cancer Pharmacology, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
authors: Shashank K
authors: SK
authors: Singh
authors: Division of Cancer Pharmacology, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
authors: Shashi
authors: S
authors: Bhushan
authors: Department of Chemistry, University of Kashmir, Hazratbal, Srinagar 190006, J&K, India.
authors: G
authors: G
authors: Mustafa Peerzada
authors: Natural Product Chemistry Division, CSIR-Indian Institute of Integrative Medicine (IIIM), Canal Road, Jammu Tawi 180001, India. Electronic address: bashah@iiim.res.in.
authors: Bhahwal Ali
authors: BA
authors: Shah
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; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D016566:Organoselenium Compounds
keywords: Anti-cancer; Apoptosis; DNA-binding; Diselenides; In silico