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.

Quinolones : Novel probes in antifilarial chemotheraphy

Abstract: Quinolones have been discovered in our laboratory as a new class of antifilarial agents. This has led to the design, synthesis, and antifilarial evaluation of a number of N-substituted quinol-4(1H)-one-3-carboxamide derivatives 4-6. The macrofilaricidal activity of the target compounds was initially evaluated in vivo against Acanthoeilonema viteae by oral administration of 200 mg/kg x 5 days. Among all the synthesized compounds, 13 displayed activity, with the most potent compound (4a) exhibiting 100% macrofilaricidal and 90% microfilaricidal activities. Compound 4e elicited significant macrofilaricidal (80%) response while compound 5c showed 100% sterilization of female worms. Finally, the two most potent macrofilaricidal compounds, namely 4a and 4e, have been screened for their potency against DNA topoisomerase II, and it has been observed that both have the capability to interfere with this enzyme at 10 micromol/mL concentration. The structure-activity relationship (SAR) associated with position-3 and aryl ring substituents is discussed.

Discovery of a new class of dithiocarbamates and rhodanine scaffolds as potent antifungal agents: synthesis, biology and molecular docking

Abstract: Drug resistance to established antifungals such as azole derivatives (fluconazole and ketoconazole) is driving the rise in global mortality due to fungal infection. Identification of new molecular entities structurally unrelated to these may represent a valid strategy to overcome resistance to currently available drugs. In an effort to develop highly potent antifungal agents, we report herein a series of 27 compounds of dithiocarbamate and the rhodanine molecules containing pyridine moiety and their antifungal activity. Among the synthesized compounds, several analogues have shown potent antifungal activity. The potent compounds against Candida albicans strain were further tested for in vitro anticandidal activity and amphotericin B-resistant strain of Candida albicans. Several derivatives 4a–f, 6, and 7k–n were found to be more effective (MIC = 0.39 – 3.12 μg mL−1) against Candida albicans MTCC183 and further these compounds, except 4e, 4f, and 7m, showed significant activity against amphotericin B-resistant strain of Candida albicans than that of fluconazole. Moreover, these analogues did not exhibit any toxicity up to MIC 3.12 μg mL−1 against mammalian cell line L929. A molecular docking study was undertaken to understand the mode of action of the active compounds towards prospective target lanosterol 14α-demethylase (CYP-51).

Diverse Roles of Extracellular Calcium-Sensing Receptor in the Central Nervous System

Abstract: The G-protein-coupled calcium-sensing receptor (CaSR), upon activation by Ca(2+) or other physiologically relevant polycationic molecules, performs diverse functions in the brain. The CaSR is widely expressed in the central nervous system (CNS) and is characterized by a robust increase in its expression during postnatal brain development over adult levels throughout the CNS. Developmental increases in CaSR levels in brain correlate with myelinogenesis. Indeed, neural stem cells differentiating to the oligodendrocyte lineage exhibit the highest CaSR expression compared with those differentiating to astrocytic or neuronal lineages. In adult CNS, CaSR has broad relevance in maintaining local ionic homeostasis. CaSR shares an evolutionary relationship with the metabotropic glutamate receptor and forms heteromeric complexes with the type B-aminobutyric acid receptor subunits that affects its cell surface expression, activation, signaling, and functions. In normal physiology as well as in pathologic conditions, CaSR is activated by signals arising from mineral ions, amino acids, polyamines, glutathione, and amyloid-beta in conjunction with Ca(2+) and other divalent cationic ligands. CaSR activation regulates membrane excitability of neurons and glia and affects myelination, olfactory and gustatory signal integration, axonal and dendritic growth, and gonadotrophin-releasing hormonal-neuronal migration. Insofar as the CaSR is a clinically important therapeutic target for parathyroid disorders, development of its agonists or antagonists as therapeutics for CNS disorder could be a major breakthrough.

Long non-coding RNAs (lncRNAs) in spermatogenesis and male infertility

Abstract: Long non-coding RNAs (lncRNAs) have a size of more than 200 bp and are known to regulate a host of crucial cellular processes like proliferation, differentiation and apoptosis by regulating gene expression. While small noncoding RNAs (ncRNAs) such as miRNAs, siRNAs, Piwi-interacting RNAs have been extensively studied in male germ cell development, the role of lncRNAs in spermatogenesis remains largely unknown. In this article, we have reviewed the biology and role of lncRNAs in spermatogenesis along with the tools available for data analysis. Till date, three microarray and four RNA-seq studies have been undertaken to identify lncRNAs in mouse testes or germ cells. These studies were done on pre-natal, post-natal, adult testis, and different germ cells to identify lncRNAs regulating spermatogenesis. In case of humans, five RNA-seq studies on different germ cell populations, including two on sperm, were undertaken. We compared three studies on human germ cells to identify common lncRNAs and found 15 lncRNAs (LINC00635, LINC00521, LINC00174, LINC00654, LINC00710, LINC00226, LINC00326, LINC00494, LINC00535, LINC00616, LINC00662, LINC00668, LINC00467, LINC00608, and LINC00658) to show consistent differential expression across these studies. Some of the targets of these lncRNAs included CENPB, FAM98B, GOLGA6 family, RPGR, TPM2, GNB5, KCNQ10T1, TAZ, LIN28A, CDKN2B, CDKN2A, CDKN1A, CDKN1B, CDKN1C, EZH2, SUZ12, VEGFA genes. A lone study on human male infertility identified 9879 differentially expressed lncRNAs with three (lnc32058, lnc09522, and lnc98497) of them showing specific and high expression in immotile sperm in comparison to normal motile sperm. A few lncRNAs (Mrhl, Drm, Spga-lncRNAs, NLC1-C, HongrES2, Tsx, LncRNA-tcam1, Tug1, Tesra, AK015322, Gm2044, and LncRNA033862) have been functionally validated for their roles in spermatogenesis. Apart from rodents and humans, studies on sheep and bull have also identified lncRNAs potentially important for spermatogenesis. A number of these non-coding RNAs are strong candidates for further research on their roles in spermatogenesis.

Antidiabetic and antidyslipidemic activities of Cuminum cyminum L. in validated animal models

Abstract: The ethanolic extract of seeds of Cuminum cyminum (C.c) was found to improve glucose tolerance to the tune of around 18.3% (P < 0.01) in normal rats and shows around 17.7% (P < 0.01) and 17.1% fall on blood glucose levels at 0–300 and 0–1440 min, respectively, on streptozotocin-induced diabetic rats at an oral dose of 250 mg/Kg body weight. The extract has also been found to improve around 26.7% (P < 0.01) glucose intolerance on 14th day post treatment in high fructose fed streptozotocin-induced diabetic rats. The extract was also found to have antidyslipidemic activity as evident by 21.04% (P < 0.01) decline in serum triglycerides, 22.7% (P < 0.01) decline in total serum cholesterol, and 16.9% of decline in serum LDL-C, respectively, along with 12.2% (P < 0.05) increase in serum HDL-C on high fat diet fed male Syrian golden hamster. The extract was also found inhibitory to eye lens aldose reductase (EC 1.1.1.21) with IC50 value of 7.07 μg/ml as compared to the standard AR inhibiting compound Quercetin which showed IC50 2.35 μg/ml. The extract was also found inhibitory to α-glucosidase with IC50 value of 100 μg/ml as compared to known drug Acarbose which showed IC50 of around 25 μg/ml.