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.

Molecular mechanisms of antimony resistance in Leishmania.

Abstract: Leishmaniasis causes significant morbidity and mortality worldwide. The disease is endemic in developing countries of tropical regions, and in recent years economic globalization and increased travel have extended its reach to people in developed countries. In the absence of effective vaccines and vector-control measures, the main line of defence against the disease is chemotherapy. Organic pentavalent antimonials [Sb(V)] have been the first-line drugs for the treatment of leishmaniasis for the last six decades, and clinical resistance to these drugs has emerged as a primary obstacle to successful treatment and control. A multiplicity of resistance mechanisms have been described in resistant Leishmania mutants developed in vitro by stepwise increases of the concentration of either antimony [Sb(III)] or the related metal arsenic [As(III)], the most prevalent mechanism being upregulated Sb(III) detoxification and sequestration. With the availability of resistant field isolates, it has now become possible to elucidate mechanisms of clinical resistance. The present review describes the mechanisms of antimony resistance in Leishmania and highlights the links between previous hypotheses and current developments in field studies. Unravelling the molecular mechanisms of clinical resistance could allow the prevention and circumvention of resistance, as well as rational drug design for the treatment of drug-resistant Leishmania.

Depletion of Reduced Glutathione, Ascorbic Acid, Vitamin E and Antioxidant Defence Enzymes in a Healing Cutaneous Wound

Abstract: In the present investigation the involvement of free radicals in a self-healing cutaneous wound has been demonstrated. The levels of different enzymatic and non-enzymatic antioxidants have been studied in 2,4,7 and 14 days old wounds and compared with normal skin. Except for glutathione reductase (GR), all other enzymatic and non-enzymatic antioxidants were found to decrease following wounding. The decrease was 60-70% in superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) at 2, 4 and 7 days, while in the case of catalase (CAT) the decrease was 40-60% during this period. Although a complete recovery in the activity of CAT was observed, SOD and GPx did not recover completely and GST was found to be slightly elevated on 14th day post wounding. Non-enzymatic antioxidants viz, ascorbic acid, vitamin E and glutathione were also found to decrease to about 60-70% and except glutathione none of them was found to recover completely at 14th day postwounding. Interestingly thiobarbituric acid reactive substance (TBARS) expressed as malondialdehyde (MDA) equivalent, a marker of lipid peroxidation, decreased following wounding which could be because of meagre availability of lipid substrate and/or of ascorbic acid. The results indicate that wounding results in loss of different free radical scavengers both enzymatic and non-enzymatic which either partially or completely recover following healing.

Synthetic methodologies of achiral diarylmethanols, diaryl and triarylmethanes (TRAMs) and medicinal properties of diaryl and triarylmethanes-an overview

Abstract: The last decade has witnessed a high demand of various synthetic approaches towards bioactive achiral diarylmethanols, diaryl and triarylmethanes and the molecules derived thereof. Their biological and therapeutical relevancy in diverse areas such as antimicrobials, infectious, cardiovascular and nervous system disorders, genital tract diseases, estrogen related disorders and bone remodeling is quite well known. These small molecules have also been the starting materials for the development of a variety of pharmaceutically important compounds. Compounds belonging to this family have not only played a leading role in the development of small molecules as therapeutically useful compounds but also have become one of the mainstays for the development of organic synthesis. However, a comprehensive review which covers their synthesis as well as their biological activity is still lacking. (Two reviews cover the synthesis of chiral diarylmethanols through asymmetric aryl transfer, and three reviews cover the photochemical properties of triarylmethanes, bioconjugation, application of trityl ions and the use of triarylmethanes as dyes.) This review describes the synthesis as well as the biological activities of this group of molecules that came up in the last fifteen years (1995–2013). The current review will cover the various approaches followed for the synthesis of achiral diarylmethanols and the strategies followed for the synthesis of achiral diaryl as well as triarylmethanes. Finally, we will also cover the bioactivities of molecules containing the diaryl and triaryl methane core.