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: Catalysis & Leishmania donovani. 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.

Induction of Mitochondrial Dysfunction and Oxidative Stress in Leishmania donovani by Orally Active Clerodane Diterpene

Abstract: This study was performed to investigate the mechanistic aspects of cell death induced by a clerodane diterpene (K-09) in Leishmania donovani promastigotes that was previously demonstrated to be safe and orally active against visceral leishmaniasis (VL). K-09 caused depolarization of the mitochondrion and the generation of reactive oxygen species, triggering an apoptotic response in L. donovani promastigotes. Mitochondrial dysfunction subsequently resulted in the release of cytochrome c into the cytosol, impairing ATP production. Oxidative stress caused the depletion of reduced glutathione, while pretreatment with antioxidant N-acetyl cysteine (NAC) was able to abrogate oxidative stress. However, NAC failed to restore the mitochondrial membrane potential or intracellular calcium homeostasis after K-09 treatment, suggesting that the generation of oxidative stress is a downstream event relative to the other events. Caspase-3/-7-like protease activity and genomic DNA fragmentation were observed. Electron microscopy studies revealed gross morphological alterations typical of apoptosis, including severe mitochondrial damage, pyknosis of the nucleus, structural disruption of the mitochondrion-kinetoplast complex, flagellar pocket alterations, and the displacement of organelles. Moreover, an increased number of lipid droplets was detected after K-09 treatment, which is suggestive of altered lipid metabolism. Our results indicate that K-09 induces mitochondrial dysfunction and oxidative stress-mediated apoptotic cell death in L. donovani promastigotes, sharing many features with metazoan apoptosis. These mechanistic insights provide a basis for further investigation toward the development of K-09 as a potential drug candidate for VL.

The apicoplast of Plasmodium falciparum is translationally active.

Abstract: Summary Apicoplast, the plastid-like organelle of apicomplexan parasites, has generated interest as a putative drug target. Although transcripts for genes encoded by the 35 kb circular plastid DNA have been detected, the actual presence of their protein products has only been postulated. We provide evidence for translation of the tufA gene encoded by the Plasmodium falciparum apicoplast genome. Translation elongation factor Tu (EF-Tu), the product of tufA, was localized within the organelle. TufA was found to express maximally in the trophozoite stage of the intraerythrocytic cycle. Additionally, the drug thiostrepton that has a binding site in apicoplast LSU rRNA, reduced P. falciparum apicoplast EF-Tu levels thus strengthening the view that translation in the apicoplast is the site of action of this drug.

Gold-Catalyzed Sequential Alkyne Activation: One-Pot Synthesis of NH-Carbazoles via Cascade Hydroarylation of Alkyne/6-Endo-Dig Carbocyclization Reactions

Abstract: A simple and efficient one-pot protocol for the synthesis of NH-carbazoles has been described. The strategy comprises a one-pot reaction involving the treatment of 2-alkynyl indoles with arylacetyl...