Synthesis and antileishmanial activity of piperoyl-amino acid conjugates.
Based on reported antileishmanial activity of naturally occurring alkaloid piperine and amino acid esters, their conjugates were synthesized by the hydrolysis of piperine to piperic acid followed by reaction with amino acid methyl esters. These conjugates were further converted to compounds with free carboxyl group and those with reduced double bonds. The synthesized compounds were evaluated for activity against promastigote and amastigote forms of L. donovani in vitro. All the compounds showed better activity than either piperine or the amino acid methyl esters. Piperoyl-valine methyl ester was the most active compound showing an IC50 of 0.075 mM against the amastigotes. Two active compounds were evaluated for in vivo activity in golden hamster model of leishmaniasis.
Singh
Inder Pal
IP
Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER)1, Sector 67, S.A.S. Nagar, Punjab 160062, India. ipsingh@niper.ac.in
Jain
Shreyans Kumar
SK
Kaur
Amandeep
A
Singh
Sukhvinder
S
Kumar
Rajender
R
Garg
Prabha
P
Sharma
Shyam Sundar
SS
Arora
Sunil Kumar
SK
D000470:Alkaloids / Q000737:chemistry*; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D052117:Benzodioxoles / Q000737:chemistry*; D020134:Catalytic Domain; D006224:Cricetinae; D004952:Esters / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy; D008297:Male; D008958:Models, Molecular; D010880:Piperidines / Q000737:chemistry*; D053284:Polyunsaturated Alkamides / Q000737:chemistry*
D000470:Alkaloids; D000596:Amino Acids; D000981:Antiprotozoal Agents; D052117:Benzodioxoles; D004952:Esters; D010880:Piperidines; D053284:Polyunsaturated Alkamides; C008922:piperine