Synthesis and evaluation of 1-benzhydryl-sulfonyl-piperazine derivatives as inhibitors of tumor growth and tumor angiogenesis of mouse ehrlich ascites tumor in vivo.
A series of novel 1-benzhydryl-sulfonyl-piperazine derivatives 3(a-e) were synthesized by nucleophilic substitution reaction of 1-benzhydryl-piperazine with different sulfonyl chlorides and were characterized by 1H NMR, LC/MS, FTIR and elemental analysis. In the present study, the compounds 3(a-e) exhibited in vivo inhibition of Ehrlich ascites tumor (EAT) cell growth and increased the Median Survival Time (MST) and %ILS of EAT bearing mice. Further treatment of derivatives in vivo resulted in reduction of EAT cell number and ascites formation. The efficacy of the derivatives to inhibit the angiogenesis in vivo was evaluated in tumor bearing mice peritoneum and chorio allantoic membrane (CAM) model. The compounds suppressed the blood vessel formation in vivo in mice peritoneum and in CAM. Among the compounds studied, 3e demonstrated highest tumor inhibitory and anti-angiogenic effects against mouse tumor. However, this phenomenon needs detailed investigation.
Kumar
C S Ananda
CS
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore, India, 570006.
Chandru
H
H
Sharada
A C
AC
Thimmegowda
N R
NR
Prasad
S B Benaka
SB
Kumar
M Karuna
MK
Rangappa
K S
KS
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D001559:Benzhydryl Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000378:metabolism; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D010537:Peritoneum / Q000098:blood supply / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D001559:Benzhydryl Compounds; D010879:Piperazines