Nigar Fatma

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.

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 50 mg/kg (i.p.) respectively given for 5 days. By the oral route, at 100 mg/kg for 5 days the compound caused 50.9 and 57% mortality of adult L. carinii and A. viteae, respectively. At 200 mg/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 250 mg/kg, p.o. The compound was active in vitro at 100 μg/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.

Chemotherapy of experimental filariasis: enhancement of activity profile of ivermectin with immunomodulators.

The effect of certain immunopotentiators (Freunds complete adjuvant, picroliv, tuftsin and CDRI Compound 86/448) was evaluated on exertion of antifilarial activity of ivermectin at different dose levels in cotton rats experimentally infected with Litomosoides carinii. Ivermectin alone (up to 250 micrograms/kg p.o. x 5 days) caused sterilization of most of the surviving female parasites, but had no lethal effect on adult worms. In combination with immunomodulators, ivermectin brought about significant lethal effect on adult parasites even at a dose of 1 microgram/kg x 5 days. Nevertheless, in animals receiving FCA alone, sterility was caused in > 50% of female parasites. Other immunomodulators used alone had a suppressive effect on microfilaraemia only. Immunomodulators alone or in combination with ivermectin also caused enhanced filaria-specific antibody response.

SYNTHESIS OF NEOEUDISTOMIN ANALOGS AS POTENTIAL FILARICIDES

Abstract Utilizing Pictet-spengler cyclisation, derivatives of neoeudistomin, 1-(furan-2-yl/thien-2-/3-yl/pyrrol-2-yl)-9H-pyrido[3,4-b]indoles have been synthesized. These compounds exhibited promising filaricidal activity, in vivo against Litomosoides carinii and Acanthocheilonema viteae in rodents.

1,1′-Dicyano-2-substituted ethylenes: A new class of glucose uptake inhibitors in antifilarial chemotherapy☆

Several 1,1′-dicyano-2-substituted ethylenes (2–16) were synthesized and evaluated for in vivo antifilarial activity. Some of the screened compounds showed significant antifilarial response against Acanthocheilonema viteae in rodents.

1H Magnetic resonance imaging and 31P magnetic resonance spectroscopy in experimental filariasis

1H Magnetic resonance imaging and 31P magnetic resonance spectroscopy (MRS) have been carried out in experimental rodent filariasis, i.e., Acanthocheilonema viteae infection in the rodent host, Mastomys coucha. The T2-weighted image of the infected host shows fine hyperintense thread like structures of adult filariid nests in the cervical region. 31P MRS of normal and infected hosts, localized over the same region of interest, show seven major peaks corresponding to phosphomonoesters (including glucose-6-phosphate, fructose-6-phosphate, fructose-1-6-diphosphate, phosphorylcholine, and adenine monophosphate or AMP), inorganic phosphate, glycerophosphorylcholine, phosphoenolpyruvate, phosphocreatine and nucleoside di- and tri-phosphates. Concentrations of phosphomonoesters (PMEs) are higher in the normal rodent compared with the infected ones. In vivo 31P MRS provides a non-invasive assessment of tissue bioenergetics and phospholipid metabolism.

In vivo potent antifilarial β-carbolines

Abstract 1-Methoxycarbonyl/carboxamido/cyano-9H-pyrido (3,4-b) indoles have been found to exhibit interesting in vivo filaricidal activity against Litomosoides carinii and Acanthocheilonema viteae in rodents.

Chemotherapy of Filariasis -On the Search of New Agents Effective on the Reproductive System of Female Adult Worms

The design and synthesis of a series of alkyl 5(6)-substituted benzimidazole-2-carbamates (1-13), 7-chloro-4-(4-substituted phenyl)aminoquinolines (14-16), l,2-dim ethyl-3-m ethoxycarbonyl- 4,5-disubstituted pyrroles (17-19) and some compounds belonging to the class pimelonitrile (20), dihydroquinoline (21), pyridine (22), pyridoquinoline (23) and tetrahydropyrimidine (24) have been carried out as possible antifilarial agents. All these compounds have been evaluated for their activity against male and female adult worms of Litomosoides carinii in cotton rats. The effect of these compounds was also observed on the reproductive system (condition of developing microfilariae and their release from uterus) of adult female worms. In this study, three types of compounds were discovered: (a) those which showed activity on both the male and female adult worms and also had sterilizing effects on surviving adult females (1 -3 , 6 - 9 , 13, 19), (b) those which only sterilized the adult females (14-16 , 21, 24), and (c) those which had no effect on female reproduction but killed only adult worms (4, 5, 11, 12, 17,18, 20, 22, 23). This tends to open up a new avenue in the chemotherapy of filariasis and the future scope of work on chemosterilization of adult females has been discussed.

Structure-antifilarial activity relationship of 5/6/7/8-mono- or disubstituted 1H/1-phenyl-9H-pyrido[3,4-b]indoles--a new class of potential filaricides.

Antifilarial activity of 5/6/7/8-mono-or disubstituted 1 H /1-phenyl-9H -pyrido[3,4-b]indoles (I) has been described. The 1,6-and 8 -substituted 9H-pyrido[3,4-b]indoles (I) elicited interesting filaricidal activity against Litomosoides carinii and Acanthocheilonema viteae in rodent hosts