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D Subrahmanyam

Publications and source records attributed to D Subrahmanyam.

At least 19 recordsLinked to original sources
PubMed2006

Substituent activity relationship studies on new azolo benzoxazepinyl oxazolidinones.

In an effort to discover potent antibacterials based on the entropically favored 'bioactive conformation' approach, a series of novel tricyclic molecules mimicking the conformationally constrained structure of Linezolid is reported. Based on the initial tricyclic molecule 1, the benzazepine derivative 2 was designed where the tricyclic structure had more flexibility around C-N bond compared to 1. While, the molecule 2 was less active, the molecule 3 showed promising antibacterial activity presumably after having obtained rigidity due to pyrrole ring. The syntheses, SAR studies, and evaluation of 3 as a lead compound are reported.

Anti-Bacterial Agents↗
PubMed1999

9-Deoxopodophyllotoxin derivatives as anti-cancer agents.

Several 9-deoxo-9-substituted podophyllotoxin derivatives were synthesised starting from naturally occuring podophyllotoxin and their anti-cancer activity was evaluated against in vitro human cancer cell line assay. It was observed that these compounds do possess good anti-cancer activity particularly against ovarian, renal and lung cancer cell lines.

Antineoplastic Agents↗
PubMed1999

In vitro cytotoxicity of 5-aminosubstituted 20(S)-camptothecins. Part 1.

A number of 5-aminosubstituted 20(S)-camptothecin analogues were prepared via semi-synthesis starting from 20(S)-camptothecin and 9-methoxy 20(S)-camptothecin. In vitro anti-cancer activity of these analogues was determined using 60 human tumor cell line assay. Although water solubility of most of these compounds was improved compared to 20(S)-camptothecin, their anti-cancer activity was considerably diminished. However, only smaller substituents such as methylamine or hydroxylamine as present in 8s and 8t, respectively, showed good activity with improved water solubility.

Antineoplastic Agents↗
PubMed1998

Novel D-ring analogues of podophyllotoxin as potent anti-cancer agents.

Several D-ring modified analogues of podophyllotoxin were prepared viz semi-synthesis starting from naturally occurring podophyllotoxin and determined their in vitro anti-cancer activity. Most of the analogues have shown good activity towards human cancer cell lines.

Antineoplastic Agents↗
PubMed1992

Effect of carrageenan on the resistance of congenitally athymic nude and normal BALB/c mice to infective larvae of Brugia malayi.

Resistance of BALB/c mice to infective third-stage larvae (L3) of the human filarial parasite Brugia malayi is thymus-dependent, although the actual effector mechanisms that mediate larval killing are unknown. The present study examined the effect of carrageenan (CGN) on the mechanisms of resistance to B. malayi infection in heterozygous (nu/+) and nude (nu/nu) mice. Mice were treated with CGN at a single dose of 20 or 200 mg/kg and were inoculated intraperitoneally 1 day later with 100 L3. The results showed a dose-dependent increase in the numbers of L4 and L5 that were recovered from nu/+ and nu/nu mice. CGN treatment also enhanced the recovery of mature adult worms from nu/nu mice and appeared to abolish partially the dichotomy of resistance between the usually more susceptible male and the more resistant female nu/nu mouse. Microfilariae were found in the peripheral blood and the peritoneal cavity of CGN-treated male and female nu/nu mice and in the peritoneal cavity of male but not female nu/+ mice. Fewer larval granulomas were recovered from the peritoneal cavity of treated mice. CGN-treated, parasitized nu/+ and nu/nu mice showed high titers of IgM and IgG antibodies. An experimental compound, CGP 20376, showed 100% larvicidal activity following the administration of a single dose of 20 mg/kg to CGN-treated mice. From this study, we conclude that macrophages alone or in conjunction with other cells are actively involved in the resistance of mice to B. malayi L3.

Animals↗
PubMed1991

Brugia malayi and Acanthocheilonema viteae: antifilarial activity of transglutaminase inhibitors in vitro.

The possible involvement of transglutaminase-catalyzed reactions in survival of adult worms, microfilariae (mf), and infective larvae of the filarial parasite Brugia malayi was studied in vitro by using the specific pseudosubstrate monodansylcadaverine (MDC) and the active-site inhibitors cystamine or iodoacetamide. These inhibitors significantly inhibited parasite mobility in a dose-dependent manner. This inhibition was associated with irreversible biochemical lesions followed by filarial death. A structurally related, inactive analog of MDC, dimethyldansylcadaverine, did not affect the mobility or survival of the parasites. Adult worms failed to release mf when they were incubated in the presence of MDC or cystamine, and this inhibitory effect on mf release was concentration dependent. Similar embryostatic and macrofilaricidal effects of MDC were observed in Acanthocheilonema viteae adult worms. These studies suggest that transglutaminase-catalyzed reactions may play an important role in the growth, development, and survival of filarial parasites.

Animals↗
PubMed1991

Detection of Wuchereria bancrofti specific antigens in the serum of endemic residents.

A sandwich enzyme-linked immunosorbent assay (s-ELISA) is developed for detecting circulatory antigens in individuals infected with Wuchereria bancrofti in an endemic area using antibody (Ig) against excretory-secretory-metabolic antigens of the microfilariae raised in rabbit (anti-mf-ESM) and labelled with alkaline phosphatase (ESM-Ig-conjugate). An optical density reading of a sample greater than 0.075 (after subtracting the background) was taken as positive in the s-ELISA. When homologous (WbmfESM) and heterologous (sonicated antigens of human and model intestinal helminths-Ascaris lumbricoides. Trichuris muris, Necator americanus and Strongyloides ratti) antigens were spiked at 2.5, 5, and 7.5 microgram/well, rabbit ESM-Ig-conjugate reacted specifically with the samples containing homologous antigens. Amongst 21 sera in five different categories of non-endemic group, only four (two in helminth-ve and two in mixed intestinal helminthic group) were found to be positive. Out of 19 sera from endemic residents, three of 7 endemic normals (ENS), all microfilaraemics (mf+) (n = 7) and 4 out of 5 elephantoid patient sera were positive. This preliminary data show that rabbit mfESM-Ig-conjugate is efficient in detecting sera samples containing antigenic components of microfilariae. This assay was found to be discriminatory in detecting individuals carrying current infection. This test requires further validation with larger number of samples and it may prove of value for detecting lymphatic filarial infection.

Animals↗
PubMed1991

Effect of CGP 20376 on Brugia malayi and parasite antigenemia in jirds.

This study was designed to investigate the activity of CGP 20376, a benzothiazole derivative, against Brugia malayi in jirds and to illustrate the utility of parasite antigen detection as a means of monitoring drug efficacy in filariasis. Drug treatment was 100% effective in jirds treated 3 or 24 days after infection. Microfilaria and adult worm counts were reduced (relative to counts in sham-treated control animals) by 96% and 95%, respectively, in animals treated 153 days after infection. Four of 6 animals in this treatment group cleared their microfilaremias and were free of adult worms 5 mo after treatment. Thus, CGP 20376 was effective against all life cycle stages of B. malayi in jirds. Parasite antigen levels in jird sera were consistent with parasitological results in all treatment groups, but antigen clearance was incomplete in some cases after apparently successful treatment of mature and immature infections.

Animals↗
PubMed1990

Effect of ivermectin on filariae of Mastomys natalensis.

The efficacy of ivermectin (Iv) was evaluated against four species of filariae, Litomosoides carinii, Acanthocheilonema viteae, Brugia pahangi and Brugia malayi in Mastomys natalensis. Animals with patent infections, induced with L3 larvae, by intravenous (iv) infusion of the respective microfilariae (Mf) (5 x 10(4) Mf per animal) or by intraperitoneal (ip) route (2 x 10(4) Mf per animal) were used in this study. A single dose of Iv (100 micrograms.kg-1) given subcutaneously (sc) to Mastomys infected with L. carinii or A. viteae resulted in the disappearance of microfilaremia within 2 h of treatment. Iv treatment of sc-infected animals with Brugia spp. had no immediate effect on the circulating Mf 60 days post-treatment. In contrast, such treatment of animals infected with Mf by intravenous infusion completely eliminated the larvae of all four species from the circulation. Iv treatment had no significant effect on the Mf of L. carinii, B. pahangi and B. malayi in animals infected by the ip route. However, the drug had dramatic effect in killing the Mf of A. viteae in the peritoneal cavity. Sera from Iv-treated normal or from L. carinii- or A. viteae-infected Mastomys were effective in clearing the circulating Mf of the species when administered to animals with the respective infections. Similar rapid clearance of Mf was seen when the sera were administered to animals infected iv with these larvae. Furthermore, adult females of L. carinii and A. viteae recovered from Mastomys on different days after Iv treatment released smaller numbers of Mf in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

IgG response of rats to the excretory-secretory products of Litomosoides carinii.

The nature of antibody responses to the excretory-secretory (ES) products of adult worms and microfilariae (Mf) of Litomosoides carinii in albino rats and their possible role in protection have been studied. Rats were immunized with ES products derived from in vitro incubation of adults or Mf. The sera from these rats promoted neutrophil-mediated killing of Mf in vitro. The antibody responsible for the cytocidal activity was identified as IgG isotype. Indirect fluorescent antibody test showed the presence of IgG on the surface of Mf incubated in either of the immune sera. The immune sera were effective in clearing the circulating Mf in Mastomys natalensis, indicating the protective nature of the antibody. Thus, L. carinii in culture liberate functional antigens that seem to have protective potential.

Animals↗
PubMed1990

Interaction of monoclonal antibodies with cuticular antigens of filarial parasites, Brugia malayi and Wuchereria bancrofti.

Monoclonal antibodies (mAbs) have been prepared against excretory-secretory-metabolic (ESM) antigens of microfilariae (mf) of Wuchereria bancrofti (WbmfESM) and against third stage larvae (L3) of Brugia malayi (BmL3), and purified from ascites fluids with ammonium sulphate. Both antibodies were of the IgM type and did not react with phosphorycholine. The mAb against BmL3 (F46) reacted in ELISA with antigens of L3 of B. malayi, B. pahangi and W. bancrofti and of adults of B. malayi. The mAb raised against wbmfESM (F32) resembled F46 in this respect, though with a lower titer towards the antigens, and in addition reacted with the ESM-antigens of mf and of L3 of W. bancrofti. F46 was able to detect L3 antigens of filarial parasites in spiked serum samples with a detection limit of 8-16 ng in absolute amount. The antibody was found to label the cuticular portion of L3 and adults of the lymphatic parasites, and not the epicuticular surface, in immunoelectron microscopic studies. The antibody recognized a 36 kDa component of the beta-mercaptoethanol extracts of B. pahangi-adults in Western blot analysis.

Animals↗
PubMed1990

Antibody-mediated cytotoxic effects in vitro and in vivo of rat cells on infective larvae of Brugia malayi.

Albino rat macrophages and neutrophils in the presence of immune serum adhered to and promoted killing of Brugia malayi infective larvae in vitro. At a similar cell-target ratio, macrophages were more potent than neutrophils in inducing cytotoxic response to the larvae. Eosinophils were also effective in killing but only at a high cell-target ratio. The activity in the immune serum could be absorbed to and eluted from a Protein A-Sepharose column suggesting involvement of IgG antibody in the reaction. An indirect fluorescent antibody test confirmed the presence of IgG on the surface of larvae incubated in immune serum. Infective larvae were attacked by host cells within micropore chambers 16-24 h after implantation into immunized rats. Further, a strong cytotoxic response to the larvae was seen when they were introduced intraperitoneally into immune rats indicating the role of antibody and cells in vivo. We suggest that antibody-dependent cellular cytotoxicity may represent an important mechanism of parasite killing in an immune host.

Animals↗
PubMed1990

Immune response to Acanthocheilonema viteae infection in multimammate rats (Mastomys natalensis).

The multimammate rat Mastomys natalensis, when infected with the filarial parasite Acanthocheilonema viteae, develops amicrofilaraemia. Worm recovery and the duration and intensity of microfilaraemia were analysed and related to the humoral and cellular immune responses of the host by using an antibody-dependent cell-mediated cytotoxicity (ADCC) assay towards microfilariae (Mf). Mf were detected in the peripheral blood at 7 weeks post-infection (p.i.), reaching maximum levels by 20 weeks p.i., and then gradually decreasing to undetectable levels during the next 36 weeks. The cytotoxic antibodies appeared around 15-18 weeks p.i., and the serum at 36 weeks p.i. induced 70% cytotoxicity to the Mf in vitro in the presence of host cells. The IgM fraction of the immune serum from amicrofilaraemic Mastomys promoted ADCC to Mf both in vitro and in vivo. Macrophages were more potent in inducing cytotoxic effect than eosinophils and neutrophils. Platelets were ineffective in killing the Mf in the presence of immune serum. IgM antibody cleared the circulating Mf from the blood when given passively to infected Mastomys. The average recovery of adult worms was about 20% of the inoculated larvae. No live females could be recovered 56 weeks p.i. Thus protective immune responses built up over an extended period of time are elicited against the Mf and perhaps even to adults in Mastomys infected with A. viteae.

Animals↗
PubMed1990

Evaluation of in vitro released Wuchereria bancrofti third stage larval antigens for detection of Bancroftian filariasis.

Three types of in vitro released excretory, secretory and metabolic antigens of Wuchereria bancrofti third larval stage (L3ESM) are evaluated in ELISA test to detect infected individuals in the endemic area. A total of 104 reference sera are used to predict the sensitivity of these antigens. None of L3 ESM antigens, although homologous in nature, did not identify correctly the categorised reference sera. This study clearly indicated a need for defined antigens to detect W. bancrofti infection early in the endemic residents.

Animals↗
PubMed1990

Differential recognition of Brugia malayi antigens by bancroftian filariasis sera.

Individuals residing in an area endemic to Wuchereria bancrofti infection were broadly categorised as endemic normals (EN), microfilaraemics (mf + ve) and elephantoids i.e., chronic lymphatic filariasis (EL). The immune status of these three groups was examined in terms of (i) specific antibody levels; (ii) ability to induce antibody dependent cellular cytotoxicity (ADCC) to microfilariae; and (iii) ability to recognise different microfilarial antigens by immunoblotting. All three groups of endemic residents were indistinguishable in their antibody levels as measured by ELISA with B. malayi microfilarial antigen. Many endemic normal sera and most elephantoid sera exerted strong cytotoxicity against W. bancrofti microfilariae whereas none of the mf + ve sera had any such activity. Immunoblotting studies revealed that a protein with mol. wt of 79 KDa was the only one among the proteins of B. malayi microfilarial extracts that was consistently recognised by sera from all endemic residents. Endemic normal sera and elephantoid sera, which exerted maximum cytotoxicity, together specifically recognised three proteins with molecular weights 25, 58 and 68 KDa and these three proteins could be among the candidate antigens that induce resistance to filarial infection.

Animals↗