3-Piperonylsydnone. A New Type of Antimalarial Agent¹

Structural modification studies of 3‐piperonylsydnone I. synthesis of piperonyl‐substituted pyrazoles, isoxazoles, triazoles, oxadiazoles and thiadiazoles

“…Prior to the present study, modification of the length of the -CH2-chain linking the phenyl and the 5 -membered mesoionic ring system was studied. However, neither 3 -homopiperonylsydnone nor 3-(3,4-methylenedioxy)phenylsydnone displayed comparable activity (2).…”

“…Among these, the P-methoxy analog possesses about half a s much activity against P. berghei but is about twice as toxic; the trimethoxy analog, which is not toxic at the dose of 1.28 g. /kg. , has similar activity a s that of 3-phenylsydnone (2,4). The dimethoxy and dichloro analogs a r e inactive (see Table I).…”

“…3-Piperonylsydnone (I) has recently been shown to possess antimalarial activity against Plasmodium berghei in mice (2). Since the mode and site of action of I a s an antimalarial agent is still not known, structural modification studies of I may contribute some information toward the understanding of the activity of this mesoionic compound.…”

Mesoionic Sydnone: A Review in Their Chemical and Biological Properties

“…It was reported that 3-piperonylsydnone (LIV) and 3-phenylsydnone showed activity against Plasmodium berghei; the main parasite that causes malaria in mice. Nyber and Chen stated that 3-piperonylsydnone exhibited antimalarial activity when administered orally or subcutaneously at a dose of 10 mg/Kg with no toxic side effects even at a dose up to 500 mg/Kg [80]. Since 3-phenylsydnone showed less activity and higher toxicity, it was of interest for other researchers to conduct a structure-activity analysis on the antimalarial activity of sydnone and piperonyl compounds.…”

Studies on Synthesis of Some New Sydnone Containing Compounds and Their Biological Activities

“…Various elecrophilic substitution reactions such as halogenation [4][5][6][7] , nitration 8 , acylation 9,10 , sulphonation 11 occur at the fourth position of the sydnone ring containing a hydrogen atom 12 . Sydnone derivatives have been the focus of great interest because of their remarkable biological properties [13][14][15] , such as antibacterial 16,17 , antitumor 18,19 , antifungal 20,21 , antimalarial [22][23][24] , antiparasitic 25 , analgesic 26 , antioxidant 27 , anti inflammatory 28 . Sydnone derivatives also show significant response of coronary dilation test, collagen induced platelet aggregation inhibition, local anaesthetic, antiwrithing, anticonvulsant, muscle relaxation and moderate cardio tropic activity 29 .…”