Inhibition and structural insights of leishmanial glutamyl-tRNA synthetase for designing potent therapeutics.

Aminoacyl-tRNA synthetases (aaRSs), essential components of the protein synthesizing machinery, have been often chosen for devising therapeutics against parasitic diseases. Due to their relevance in drug development, the current study was designed to explore functional and structural aspects of Leishmania donovani glutamyl-tRNA synthetase (LdGluRS). Hence, LdGluRS was cloned into an expression vector and purified to homogeneity using chromatographic techniques.

Exploration of seryl tRNA synthetase to identify potent inhibitors against leishmanial parasites.

Aminoacyl-tRNA synthetases are crucial enzymes for cellular protein metabolism and have been considered as an attractive target for development of new antimicrobials. In the current study, seryl tRNA synthetase of Leishmania donovani (LdSerRS) and its mutants were purified and characterized through biochemical and structural methods. Purified LdSerRS was found to be enzymatically active and exhibited more alpha helices in secondary structure.

Biophysical and Structural Characterization of Ribulose-5-phosphate Epimerase from .

Pentose phosphate pathway (PPP) plays a crucial role in the maintenance of NADPH/NADP homeostasis and provides protection against oxidative stress through detoxification of the reactive oxygen species. Ribulose-5-phosphate epimerase (RPE) participates in catalysis of the interconversion of ribulose-5-phosphate (Ru5P) to xylulose-5-phosphate (Xu5P) during PPP, however the structural attributes of this enzyme are still underexplored in many human pathogens including leishmanial parasites. The present study focuses upon cloning, purification and characterization of RPE of (RPE) using various biophysical and structural approaches.

Biochemical and structural insights into 6-phosphogluconate dehydrogenase from Leishmania donovani.

6-phosphogluconate dehydrogenase (6PGDH) participates in pentose phosphate pathway of glucose metabolism by catalyzing oxidative decarboxylation of 6-phsophogluconate (6PG) and its absence has been lethal for several eukaryotes. Despite being a validated drug target in many organisms like Plasmodium, the enzyme has not been explored in leishmanial parasites. In the present study, 6PGDH of Leishmania donovani (Ld6PGDH) is cloned and purified followed by its characterization using biochemical and structural approaches.

Leishmanial aspartyl-tRNA synthetase: Biochemical, biophysical and structural insights.

Aminoacyl tRNA synthetases (aaRSs) are integral components of protein biosynthesis along with several non-canonical cellular processes. Inhibition studies of aaRSs presented these enzymes as promising drug targets in many pathogens, however aspartyl tRNA synthetase has not been studied in trypanosomatids despite its essentiality. Hence, full-length ORF of Leishmania donovani aspartyl tRNA synthetase (LdaspRS) was cloned and purified to homogeneity followed by molecular mass determination.

Synthesis, F-radiolabeling and apoptosis inducing studies of novel 4, 7-disubstituted coumarins.

In present study, a new series of 4, 7-disubstituted coumarin derivatives (7a-y) have been synthesized as galectin-1 targeting apoptosis inducing agents and evaluated for their in vitro cytotoxic potentials against a panel of selected human cancer cell lines namely, Brest (MCF7), Ovarian (SKOV3), Prostate (PC-3 & DU145) and normal embryonic kidney (HEK293T) cells, using MTT assay. Most of the compounds exhibited potent growth inhibitory action against the treated cancer cell lines with an IC range of 10-30 µM. Compound 7q exhibited a significant growth inhibition against prostate cancer (PC-3 & DU145) cell lines with an IC value of 7.

Structural attributes and substrate specificity of pyridoxal kinase from Leishmania donovani.

The enzyme pyridoxal kinase (PdxK) catalyzes the conversion of pyridoxal to pyridoxal-5'-phosphate (PLP) using ATP as the co-factor. The product pyridoxal-5'-phosphate plays a key role in several biological processes such as transamination, decarboxylation and deamination. In the present study, full-length ORF of PdxK from Leishmania donovani (LdPdxK) was cloned and then purified using affinity chromatography.

Protein phosphatase 1 of Leishmania donovani exhibits conserved catalytic residues and pro-inflammatory response.

Protein phosphorylation, governed by kinases and phosphatases, plays a pivotal role in enormous cellular signaling pathways. Although PPP family of serine/threonine phosphatases have been involved in multiplication and growth of trypanosomatid parasites, but comprehensive knowledge is still very limited. In the present study, protein phosphatase 1 from Leishmania donovani (LdPP1) was purified to homogeneity and its structural attributes were explored employing CD and fluorescence spectroscopy as well as bioinformatics methods.

Synthesis of 1-benzyl-1H-benzimidazoles as galectin-1 mediated anticancer agents.

In our pursuit to develop novel non-carbohydrate small molecule Galectin-1 Inhibitors, we have designed a series of 1-benzyl-1H-benzimidazole derivatives and demonstrated their anticancer activity. The compound 6g, 4-(1-benzyl-5-chloro-1H-benzo[d]imidazol-2-yl)-N-(4-hydroxyphenyl) benzamide was found to be most potent with an IC of 7.01 ± 0.

Synthesis and biological evaluation of morpholines linked coumarin-triazole hybrids as anticancer agents.

A series of novel morpholines linked coumarin-triazole hybrids (6a-6v) has been synthesized and evaluated for their anti-proliferative potential on a panel of five human cancer cell lines, namely bone (MG-63), lung (A549), breast (MDA-MB-231), colon (HCT-15) and liver (HepG2), using MTT assay. Among all, the compound 6n {7-((1-(2,4-dichlorobenzyl)-1H-1,2,3-triazol-4-yl) methoxy)-4-((2,6-dimethylmorpholino) methyl)-2H-chromen-2-one} showed significant growth inhibition against MG-63 cells with an IC value of 0.80 ± 0.

Leishmania donovani PP2C: Kinetics, structural attributes and in vitro immune response.

Most of the signaling pathways are regulated by reversible phosphorylation-dephosphorylation which involves enzymes- kinases and phosphatases. Current knowledge about the protein phosphatases in parasites like Trypanosoma and Leishmania is very minimal despite their enormousity. In present study, full length ORF of Leishmania donovani PP2C was cloned into expression vector followed by purification and molecular weight determination using Ni-NTA affinity and gel giltration chromatography respectively.