P.M.S. Chauhan

Present trends and future strategy in chemotherapy of malaria

This review starts from a brief introduction followed by the list of commercial antimalarial drug. According to the nature of chemical entities, these drugs have been divided into the following categories--Quinolines, pyrimidines, amidinies, guanidines, sulfonamides, sulfones, acridines, antibiotics and sesquiterpene lactones. The site of action and status of the antimalarial drugs have been described against each category. A brief description of reasons behind the search of a new antimalarial drug have been discussed. Finally, the review deals the well known biochemical target sites such as folate metabolism, pyrimidine metabolism and polyamines for the designing of antimalarial drugs. The detail description of the newly discovered biochemical target sites, alpha-tublin and DNA topoisomerases, have been highlighted. In the conclusion section, we have discussed the future strategies for the chemotherapy of malaria.

Syntheses and antifilarial profile of 7-chloro-4-(substituted amino) quinolines: a new class of antifilarial agents ☆

The syntheses of 7-chloro-4-(substituted amino) quinolines (2-22) and their antifilarial activities are delineated. Some of the screened compounds have shown promising filarial response and sterilization effect on female Acanthocheilonema viteae in rodents.

Solid phase synthesis of structurally diverse pyrimido[4,5-d] pyrimidines for the potential use in combinatorial chemistry

An efficient solid phase synthesis of pyrimido[4,5-d]pyrimidine derivatives is described. Reaction of polymer-bound pyrimidine 1 with urea or thiourea followed by cleavage from the support provided 4-aminopyrimido[4,5-d]pyrimidines 4 and 5 while treatment of 6 with phenyl isocyanate or phenyl isothiocyanate followed by cleavage from resin afforded 3-phenylpyrimido[4,5-d]pyrimidines 9 and 10.

A NOVEL STRATEGY FOR N-ALKYLATION OF PRIMARY AMINES

Abstract N-alkyiation of primary amines has been carried out with alkylbromide using commercial Me2SO and K2CO3 as a base. This process offers a method of selection for obtaining either mono or dialkyl amines.

Syntheses and antifilarial profile of 5-amino and 5,8-diamino-isoquinoline derivatives: A new class of antifilarial agents

Abstract The syntheses of 5-amino (4–12,15) and 5,8-diamino(16–17) isoquinoline derivatives. their antifilarial activity and their effect on metabolic activities of filariids are delineated. Some of the screened compounds have shown promising filaricidal response against Acanthocheilonema viteae in rodents.

Synthesis of bisquinolines and their in vitro ability to produce methemoglobin in canine hemolysate

Synthesis of a number of derivatives of bisquinolines (3-9) have been reported here. Effect of these compounds on in vitro methemoglobin formation and methemoglobin reductase activity has resulted in the identification of two potential compounds (5 & 7), showing negligible methemoglobin toxicity.

Synthesis of 7-chloro-4-substituted aminoquinolines and their in vitro ability to produce methemoglobin in canine hemolysate

Abstract Synthesis of aminoquinoline derivatives (2–15) and their in vitro effects on methemoglobin formation and methemoglobin reductase activity are delineated. Some of the screened compounds have shown considerable methemoglobin toxicity.

Secondary amines as new pharmacophores for macrofilaricidal drug design.

Several secondary amines exhibit promising macrofilaricidal response in vivo through oral route of administration against Acanthocheilonema viteae in which N-hexylcyclohexylamine (1) shows 100% macrofilaricidal activity while a tertiary amine such as 9 elicits predominantly microfilaricidal (93%) response.

Antifilarial activity of a synthetic marine alkaloid, aplysinopsin (CDRI Compound 92/138)

CDRI Compound 92/138, a synthetic analogue of aplysinopsin, was evaluated in experimental filarial infections, Litomosoides carinii in cotton rats (Sigmodon hispidus) and Acanthocheilonema viteae in Mastomys coucha. The compound killed 63.8 and 90% of adult L. carinii and A. viteae at doses of 30 and 50u2003mg/kg (i.p.) respectively given for 5 days. By the oral route, at 100u2003mg/kg for 5 days the compound caused 50.9 and 57% mortality of adult L. carinii and A. viteae, respectively. At 200u2003mg/kg administered orally on days 0, 10 and 25 post‐infection, it reduced establishment of adult A. viteae by 68.5%. We also found 43.7 and 37.8% effect in vivo respectively on L3 and L4 stages of A. viteae at a single dose of 250u2003mg/kg, p.o. The compound was active in vitro at 100u2003μg/ml concentration and caused a significant decline in MTT reduction and 14C‐glucose uptake by adult filariids. Thus synthetic marine aplysinopsin could provide a new pharmacophore for the development of antifilarial agents.

Solid phase synthesis of quinolones

Solid phase syntheses of ethyl 6-carboxyquinol-4(1H-)-one-3-carboxylate (5) and N-substituted 6-carboxyquinol-4(1H)-one-3-carboxamides 7a-d have been described. Antifilarial in vitro activities of 5,7a-d against Brugia malayi have also been delineated.