title: Synthesis and anticancer potential of benzothiazole linked phenylpyridopyrimidinones and their diones as mitochondrial apoptotic inducers.
abstract: A series of benzothiazole linked phenylpyridopyrimidinones (8a-g) and their diones (9a-g) have been designed, synthesized and evaluated for their anticancer activity. Among the series one of the conjugate 8b showed significant cytotoxicity against human cervical cancer cell line ME-180 with IC50 value of 4.01μM. This compound was tested on the cell cycle perturbations and DNA damage. Flow cytometry analysis revealed that the compound 8b showed drastic cell cycle perturbations due to concentration dependent increase in the sub-G0 phase in ME-180 cell line. DNA fragmentation and Hoechst staining reveals that this compound induced cell death by apoptosis. Further caspase-3 and loss of mitochondrial membrane potential suggested that the compound induces cell death by apoptosis.
authors: Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India. Electronic address: ahmedkamal@iict.res.in.
authors: Ahmed
authors: A
authors: Kamal
authors: Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India.
authors: Md
authors: M
authors: Ashraf
authors: Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India.
authors: M V P S
authors: MV
authors: Vishnu Vardhan
authors: Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India.
authors: Shaikh
authors: S
authors: Faazil
authors: Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India.
authors: V Lakshma
authors: VL
authors: Nayak
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects*; D015394:Molecular Structure; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D052160:Benzothiazoles; D011744:Pyrimidinones; C005465:benzothiazole
keywords: Benzothiazole linked-phenylpyridopyrimidinone; Cell cycle arrest; Cytotoxicity