Synthesis of novel 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole derivatives as antiproliferative agents: a structure-activity relationship study.
A series of novel 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole derivatives 5(a-m) were synthesized with different substituted aromatic/heterocyclic acid chlorides (R-CO-Cl) and characterized by (1)H NMR, LC/MS, FTIR and elemental analyses. All the compounds synthesised were evaluated for their antiproliferative activity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The antiproliferative effects of the synthesised compounds were tested against viable human skin fibroblast cells and carcinoma cells namely HeLa cells, HT-29 cells, MCF-7 cells, HepG-2 cells by adopting positive and negative control. The importance of the aromatic and heterocyclic moiety was confirmed. From the SAR studies, it reveals that, the substitution at N-terminal of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole by the heterocyclic ring plays a dominant role and was responsible for the antiproliferative activity. Among the synthesized compounds 5a, 5d and 5k have showed potent antiproliferative activity on all the carcinoma cells tested.
Benaka Prasad
S B
SB
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore, 570006, India.
Vinaya
K
K
Ananda Kumar
C S
CS
Swarup
Sanjay
S
Rangappa
K S
KS
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D044366:Transition Temperature / Q000187:drug effects
D000970:Antineoplastic Agents; D007555:Isoxazoles; D010880:Piperidines