Central Drug Research Institute

About: Central Drug Research Institute is a facility organization based out in Lucknow, Uttar Pradesh, India. It is known for research contribution in the topics: Leishmania donovani & Brugia malayi. The organization has 4357 authors who have published 7257 publications receiving 143871 citations. The organization is also known as: Central Drug Research Institute, Lucknow & CDRI.

Hepatoprotective Activity of Ricinus communis Leaves

Abstract: Ricinus communis (leaf extract) was evaluated for hepatoprotective, choleretic and anticholestatic activity. In a preliminary test with albino rats, an ethanol extract showed significant protection against galactosamine-induced hepatic damage. It also showed dose-dependent choleretic and anti cholestatic activity, and hepatoprotective activity as judged by hepatocytes isolated from paraceta mol-treated rats. On fractionation of the ethanol extract, maximum activity was localised in the butanol fraction. Subsequent chromatographic fractionation and testing in the galactosamine model led to the isolation of two active fractions which in turn yielded two pure compounds: ricinine and N-demethyl-ricinine. N-Demethyl-ricinine was found to be more active and it reversed the biochemical changes produced by galactosamine at a dose of 6 mg/kg x 7 days. It possessed marked choleretic activity and demonstrated an anticholestatic effect against paracetamol-induced cholestasis.

Synthesis of hybrid 4-anilinoquinoline triazines as potent antimalarial agents, their in silico modeling and bioevaluation as Plasmodium falciparumtransketolase and β-hematin inhibitors

Abstract: Analogues of a novel class of hybrid 4-anilinoquinoline triazines have been synthesized with the aim of identifying the compounds with improved antimalarial activity preserving the potency of parent drug chloroquine (CQ). All the synthesized molecules were evaluated in vitro for their antimalarial activity against chloroquine-sensitive 3D7 and chloroquine-resistant K1 strains of P. falciparum. Molecules were also screened for their cytotoxicity towards VERO cell line. Sixteen compounds (17, 19, 26, 27, 29, 31, 32, 33, 35, 36, 37, 39, 40, 49, 50, and 52) exhibited excellent antimalarial activity with IC50 values ranging from 1.36–4.63 ng ml−1 and were also found to be nontoxic with good selectivity index. In silico activity prediction as well as enzyme inhibitory activity against P. falciparumtransketolase reveals that the molecules are also good inhibitors of the enzymeP. falciparumtransketolase. The compound 52 showed good in vivo activity by oral route and resulted in survival of 3 out of 5 mice till day 28.

Merozoite surface protein 1 of Plasmodium vivax induces a protective response against Plasmodium cynomolgi challenge in rhesus monkeys.

Abstract: Progress towards a vaccine against Plasmodium falciparum malaria is advancing rapidly, with several candidate antigens being tested for safety and efficacy in humans (4); comparatively, however, the development of a vaccine against P. vivax malaria has lagged behind. Unlike P. falciparum, where sporozoite challenge studies using the chloroquine-sensitive 3D7 strain are available, the relapsing nature of P. vivax hepatic stages and the lack of an in vitro culture system precludes any sporozoite challenge studies of P. vivax vaccine candidates in humans. Therefore, as more recombinant vaccine products become available, there will be an increasing need to compare and down-select vaccine candidate antigens in preclinical studies using animal models of P. vivax infection. P. cynomolgi, which infects rhesus macaques in southeast Asia, is a closely related species to P. vivax; human transmission of P. cynomolgi has also been reported (25). The two parasites share a similar clinical course of infection (26), a reticulocyte-specific invasion (17), the presence of Schuffner's dots on infected erythrocytes (2), and a dormant liver hypnozoite stage that is responsible for a relapsing blood stage infection (23). P. cynomolgi and P. vivax have similar genomic GC content, and rRNA analysis confirms their close taxonomic relatedness (43). High homology of prime vaccine candidates such as the apical membrane antigen 1, 97% (13); circumsporozoite protein, 90% (16); erythrocyte binding protein, 76% (32); and the 42-kDa fragment of the merozoite surface protein 1 (MSP-1), 75% (31); have been reported. Although it is believed that the P. cynomolgi-rhesus model can serve as a model for testing P. vivax antigens, there is only one previous report where this model was used to test the efficacy of a recombinant P. vivax vaccine (22). The merozoite surface protein 1 (MSP-1), found on the surface of Plasmodium merozoites, has been a prime vaccine candidate for many years (10). Following its synthesis as a 200-kDa precursor, the MSP-1 molecule undergoes step-wise proteolytic processing resulting in a glycosyl-phosphatidylinositol-anchored 42-kDa protein (MSP-142) on the surface of free merozoites (7). This 42-kDa intermediate undergoes secondary processing at the time of invasion, releasing a 33-kDa soluble polypeptide (MSP-133) and leaving behind on the invading merozoite a glycosyl-phosphatidylinositol-anchored 19-kDa form (MSP-119) (7). Depending on the species, MSP-119 contains 10 or 11 cysteine residues that form five disulfide bonds. Immunization with recombinant MSP-142 and MSP-119 raises antibodies that inhibit invasion of merozoites in vitro (9) and protects the immunized animals against live parasite challenge (29). We have previously reported a process for the production of correctly folded human vaccine-grade P. vivax MSP-142 protein in the bacterial expression host Escherichia coli Origami(DE3) (14). This bacterial strain has mutations in both the thioredoxin reductase (trxB) and glutathione reductase (gor) genes, which greatly enhances the disulfide bond formation of recombinant proteins expressed in its cytoplasm, hence resulting in a soluble product (6). However, the transposon-mediated genetic modifications of E. coli carried both the tetracycline and the kanamycin resistance genes as selectable markers and therefore made the cells incompatible with the production of human use vaccines that relied on plasmids carrying the Tetr or the Kanr genes. The use of a compatible expression host E. coli BL21(DE3) resulted in the production of an MSP-142 protein that was insoluble and located in the inclusion body fraction of the cells. In this report we have shown that soluble MSP-142 protein can be obtained from the BL21(DE3) cells by in vitro refolding of the inclusion body-derived protein under controlled redox conditions. Both the soluble and refolded P. vivax MSP-142 products appeared to be structurally similar based on biophysical analysis and reactivity with conformational epitope-specific monoclonal antibodies. It was our goal, therefore, to seek evidence of the immunological equivalence of these proteins in a parasite challenge model. Towards that end we report here the results of a vaccination study comparing the immunogenicity and efficacy of the soluble and refolded P. vivax MSP-142 products in the P. cynomolgi-rhesus model. We have also produced equivalent homologous constructs of P. cynomolgi MSP-142 protein both in their soluble and refolded forms, and these two proteins were also used as positive control immunogens in this study.