Synthesis and screening of 1-methyl-4-substituted benzoyl piperazides against adult Setaria digitata for antifilarial activity.
There is no safe and effective drug for killing the adult worms for the elimination/control of lymphatic filariasis and research is very much warranted towards the development of a macrofilaricidal drug. Therefore, the synthesis and evaluation of 1-N-methyl-substituted benzoyl/phenyl acetyl piperazides for macrofilaricidal activity were carried out. The title compounds, 1-N-methyl-substituted benzoyl/phenyl acetyl piperazides were synthesized and purified by slightly modifying the reported procedure and characterized by FT-IR, NMR and mass spectral data. The compounds were screened for macrofilaricidal activity against adult Setaria digitata, the bovine filarial worm for motility and MTT reduction assays using the reported procedures. All the compounds synthesized were characterized by spectral data. Out of 26 compounds synthesized and screened for macrofilaricidal activity, six compounds exhibited moderate antifilarial activity. The structure-activity relationships are discussed. In the case of benzoyl piperazides chloro-substitution in the para position enhanced the activity compared to its substitution in meta and ortho positions. In the case of phenyl acetyl piperazides when methyl group was in the meta position it was more active than when it was in para position. In dimethyl substituted compounds, substitutions at 3, 5-positions were more effective than 2, 3 and 3, 4 substitutions.
Vector Control Research Centre (ICMR), Indira Nagar, Pondicherry 605006, India. ananthikannan@ymail.com
M
M
Kalyanasundaram
Nisha
N
Mathew
K P
KP
Paily
G
G
Prabakaran
D000818:Animals; D004353:Drug Evaluation, Preclinical; D005369:Filaricides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005370:Filarioidea / Q000187:drug effects*; D006801:Humans; D008124:Locomotion / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D050296:Microbial Viability / Q000187:drug effects; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
D005369:Filaricides; D010879:Piperazines; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue