Synthesis and biological evaluation of heteroaryl styryl sulfone derivatives as anticancer agents.
Herein we disclose a series of novel heteroaryl styryl sulfone derivatives as potential anticancer agents. Structure-activity relationships of these newly synthesised compounds were explored with respect to the significance of the position and number of nitrogen atom of the heteroaryl ring for anti-proliferative activity in human cancer cell lines. A lead compound 14f was tested against a panel of cancerous and untransformed cell lines, and found to be highly potent against cancer cells with minimal toxicity in the untransformed cells. Further mechanistic studies uncovered that 14f caused cell-cycle arrest at the G2/M phase and induced apoptosis by targeting CDC25C and Mcl-1 proteins in A2780 ovarian cells.
Centre for Drug Discovery and Development, Sansom Institute for Health Research and School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5001, Australia.
Yi
Y
Long
Centre for Drug Discovery and Development, Sansom Institute for Health Research and School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5001, Australia.
Mingfeng
M
Yu
Centre for Drug Discovery and Development, Sansom Institute for Health Research and School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5001, Australia.
Peng
P
Li
Centre for Drug Discovery and Development, Sansom Institute for Health Research and School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5001, Australia.
Saiful
S
Islam
Centre for Drug Discovery and Development, Sansom Institute for Health Research and School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5001, Australia.
Aik Wye
AW
Goh
Centre for Drug Discovery and Development, Sansom Institute for Health Research and School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5001, Australia.
Malika
M
Kumarasiri
Centre for Drug Discovery and Development, Sansom Institute for Health Research and School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5001, Australia. Electronic address: shudong.wang@unisa.edu.au.
Shudong
S
Wang
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D006841:Hydrocarbons, Aromatic; D013450:Sulfones
Anti-cancer agents; Kinase inhibitor; Non-ATP competitive inhibition; Polo-like kinase 1; Ras-driven signaling pathways