title: Synthesis and anticancer evaluation of novel triazole linked N-(pyrimidin-2-yl)benzo[d]thiazol-2-amine derivatives as inhibitors of cell survival proteins and inducers of apoptosis in MCF-7 breast cancer cells.
abstract: A series of novel triazole linked N-(pyrimidin-2yl)benzo[d]thiazol-2-amine 5a-k were synthesized and evaluated for anticancer activity against breast (MCF-7), lung (A549) and skin (A375) cancer cell lines and their cytotoxic effects were compared against normal breast epithelial cells. The effect of compounds on cell cycle of MCF-7 breast cancer cell line was investigated by FACS. Result indicated G2/M cell cycle arrest of MCF-7 cells. Further promising compounds 5b, 5g, 5h and 5i were tested for their apoptosis inducing ability as well as inhibitory activity against key proteins NF-kB, Survivin, CYP1A1, and ERK1/2 which help in cancer cell survival and proliferation. The apoptotic aspect of these compounds is further evidenced by increase in the activity of caspase-9 in MCF-7 cells. Hence these small molecules have the potential to control both the cell proliferation as well as the invasion process in highly malignant breast cancers and can be selected for further biological studies.
authors.affiliation: Fluoroorganics Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India. Electronic address: kumbhare@iict.res.in.
authors.forename: Ravindra M
authors.initials: RM
authors.lastname: Kumbhare
authors.affiliation: Fluoroorganics Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India.
authors.forename: Tulshiram L
authors.initials: TL
authors.lastname: Dadmal
authors.affiliation: School of Chemical and Biotechnology, SASTRA University, Tirumalaisamudram, Thanjavur 613401, Tamil Nadu, India.
authors.forename: M Janaki
authors.initials: MJ
authors.lastname: Ramaiah
authors.affiliation: Fluoroorganics Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India.
authors.forename: K S V
authors.initials: KS
authors.lastname: Kishore
authors.affiliation: Chemical Biology Laboratory, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India.
authors.forename: S N C V L
authors.initials: SN
authors.lastname: Pushpa Valli
authors.affiliation: Chemical Biology Laboratory, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India.
authors.forename: Sudheer Kumar
authors.initials: SK
authors.lastname: Tiwari
authors.affiliation: Fluoroorganics Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India.
authors.forename: K
authors.initials: K
authors.lastname: Appalanaidu
authors.affiliation: Fluoroorganics Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India.
authors.forename: Y Khageswar
authors.initials: YK
authors.lastname: Rao
authors.affiliation: Chemical Biology Laboratory, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India. Electronic address: manika@iict.res.in.
authors.forename: Manika Pal
authors.initials: MP
authors.lastname: Bhadra
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D061986:MCF-7 Cells; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D014230:Triazoles / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D011743:Pyrimidines; D013844:Thiazoles; D014230:Triazoles; C560953:benzo(d)thiazol-2-amine; D019363:Cytochrome P-450 CYP1A1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053453:Caspase 9; C030986:pyrimidine
keywords: Breast cancer cells; Cytotoxicity; N-(Pyrimidin-2yl)benzo[d]thiazol-2-amine; Sharpless conditions; Triazole