Synthesis and biological evaluation of novel isoxazolines linked via piperazine to 2- benzoisothiazoles as potent apoptotic agents.
Synthesis of 3-(4-((3-Phenyl-4,5-dihydroisoxazol-5-yl)methyl)piperazin-1-yl) benzoisothiazole derivatives (5a-i), which constitute a new class of isoxazolines, has been accomplished in regio-selective manner. These derivatives have been prepared by employing the reaction between substituted aldoximes (4a-i) and 3-(4-Allylpiperazin-1-yl) benzoisothiazole in presence of chloramine-T which afforded in good yields. These compounds were screened for cytotoxic activity on tumor cells. Four among the nine synthesized compounds were found to exhibit potent cytotoxic and antineoplastic activities in comparison to tumor necrosis factor-related apoptosis inducing ligand (TRAIL) protein in mammalian cancer cells. The rest of the derivatives showed moderate activity.
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India.
Sathish
S
Byrappa
Department of Studies in Biotechnology, University of Mysore, Manasagangotri, Mysore 570 006, India.
M
M
Harsha Raj
Department of Studies in Biotechnology, University of Mysore, Manasagangotri, Mysore 570 006, India.
Tenzin
T
Kungyal
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India.
Narayana U
NU
Kudva N
Department of Studies in Biotechnology, University of Mysore, Manasagangotri, Mysore 570 006, India.
Bharathi P
BP
Salimath
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India. Electronic address: kmlrai@yahoo.com.
K M
KM
Lokanatha Rai
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010879:Piperazines / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry*; D013997:Time Factors
D000970:Antineoplastic Agents; D007555:Isoxazoles; D010879:Piperazines; D013844:Thiazoles
Benzoisothiazoles; Isoxazole and cytotoxic activity; Piperazine