Structure-based drug design, synthesis and screening of MmaA1 inhibitors as novel anti-TB agents.

Tuberculosis is one of the leading causes of death across the world. The treatment regimens for tuberculosis are well established, but still the control of the disease faces many challenges such as lengthy treatment protocols, drug resistance and toxicity. In the present work, mycolic acid methyl transferase (MmaA1), a protein involved in the maturation of mycolic acids in the biochemical pathway of the Mycobacterium, was studied for novel drug discovery.

Structural insights into suppressor of cytokine signaling 1 protein- identification of new leads for type 2 diabetes mellitus.

The study considers the Suppressor of cytokine signaling 1 (SOCS1) protein as a novel Type 2 diabetes mellitus (T2DM) drug target. T2DM in human beings is also triggered by the over expression of SOCS proteins. The SOCS1 acts as a ubiquitin ligase (E3), degrades Insulin Receptor Substrate 1 and 2 (IRS1 and IRS2) proteins, and causes insulin resistance.

Identification of small molecular inhibitors for efflux protein Rv2688c of Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) is the pathogen, which causes tuberculosis. The development of multidrug-resistant and extensively drug-resistant strains in Mtb is due to an efflux mechanism of antibiotics in the bacteria. The efflux pump proteins in the bacteria are implicated in the active efflux of antibiotics.

Selective ATP competitive leads of CDK4: Discovery by 3D-QSAR pharmacophore mapping and molecular docking approach.

The discovery of ATP competitive CDK4 inhibitors is an on-going challenging task in cancer therapy. Here, an attempt has been made to develop new leads targeting ATP binding site of CDK4 by applying 3D-QSAR pharmacophore mapping and molecular docking methods The outcome of 6 leads offers a significant contribution for selective CDK4 inhibition, since they show potential binding interactions with Val, Arg, and Glu residues of CDK4, that are unique and from other kinases. It is worth noting that there is a striking similarity in binding interactions of the leads and known CDK4 inhibitors, namely Abemaciclib, Palbociclib and Ribociclib.

Targeting the ubiquitin-conjugating enzyme E2D4 for cancer drug discovery-a structure-based approach.

Cancer progression is a global burden. The incidence and mortality now reach 30 million deaths per year. Several pathways of cancer are under investigation for the discovery of effective therapeutics.

Development of an in vitro Bioassay for Recombinant Human Erythropoietin (rHuEPO) Based on Proliferative Stimulation of an Erythroid Cell Line and Analysis of Sialic Acid Dependent Microheterogeneity: UT-7 Cell Bioassay.

Determination of biological activity and its comparison with clinical behavior is important in the quality assessment of therapeutic glycoproteins. In vivo studies are usually employed for evaluating bioactivity of these glycomolecules. However, alternative methods are required to simplify the bioassay and avoid ethical issues associated with in vivo studies.

Structural Evaluation and Binding Mode Analysis of CCL19 and CCR7 Proteins-Identification of Novel Leads for Rheumatic and Autoimmune Diseases: An Insilico study.

The Human Chemokine (C-C motif) ligand 19 (CCL19) protein plays a major role in rheumatic and autoimmune diseases. The 3D models of the CCL19 and its receptor CCR7 are generated using homology modeling and are validated using standard computational protocols. Disulfide bridges identified in 3D model of CCL19 protein give extra stability to the overall protein structure.

Identification of New Lead Molecules Against UBE2NL Enzyme for Cancer Therapy.

Cancer is characterized by abnormal growth of cells. Targeting ubiquitin proteins in the discovery of new anticancer therapeutics is an attractive strategy. The present study uses the structure-based drug discovery methods to identify new lead structures, which are selective to the putative ubiquitin-conjugating enzyme E2N-like (UBE2NL).

Identification of Novel Antagonists for Rab38 Protein by Homology Modeling and Virtual Screening.

Background: The Rab family proteins are involved in membrane trafficking, cell growth and differentiation. Rab38 is implicated in the biogenesis of melanosomes that help in the synthesis, storage and transport of melanin pigments. The Rab38 protein is overexpressed at the RNA level in melanoma cancer.

Design of novel lead molecules against RhoG protein as cancer target - a computational study.

Cancer is a class of diseases characterized by uncontrolled cell growth. Every year more than 2 million people are affected by the disease. Rho family proteins are actively involved in cytoskeleton regulation.

Homology modeling and virtual screening studies of FGF-7 protein-a structure-based approach to design new molecules against tumor angiogenesis.

Keratinocyte growth factor (KGF) protein is a member of the fibroblast growth factor (FGF) family, which is also known as FGF-7. The FGF-7 plays an important role in tumor angiogenesis. In the present work, FGF-7 is treated as a potential therapeutic target to prevent angiogenesis in cancerous tissue.

Virtual screening studies to identify novel inhibitors for Sigma F protein of Mycobacterium tuberculosis.

Tuberculosis (TB) is one of the oldest threats to public health. TB is caused by the pathogen Mycobacterium tuberculosis (MTB). The Sigma factors are essential for the survival of MTB.

Homology modeling and virtual screening of ubiquitin conjugation enzyme E2A for designing a novel selective antagonist against cancer.

Cancer is a major health problem in the world. The initiation and progression of cancer is due to imbalance between the programmed cell growth and death. These processes are triggered by the ubiquitin family enzymes.

Cellular uptake, cytotoxicity, apoptosis, DNA-binding, photocleavage and molecular docking studies of ruthenium(II) polypyridyl complexes.

Three new mononuclear [Ru (phen)2 ptip](2+) (1), [Ru (bpy)2 ptip](2+) (2) and [Ru (dmb)2 ptip](2+) (3) [ptip=(2-(5-phenylthiophen-2-yl)-1H-imidazo[4, 5-f][1,10 phenanthroline, phen=1, 10 phenanthroline, bpy=2, 2' bipyridine, dmb=4, 4'-dimethyl 2, 2' bipyridine] complexes were synthesized and characterised by elemental analysis, IR, NMR and Mass spectra. The DNA-binding behaviours were investigated by electronic absorption titration, luminescence spectra, viscosity measurements and photo-activated cleavage. The DNA-binding constants Kb of complexes 1, 2 and 3 were determined to be 7.

Macromolecular structure and interaction studies of SigF and Usfx in Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) is an intracellular human parasite that causes tuberculosis (TB). The parasite is capable of surviving under stress conditions. The gene expression in Mtb is regulated by sigma factor family of proteins.

Identification of novel leads applying in silico studies for Mycobacterium multidrug resistant (MMR) protein.

Multidrug efflux mechanism is the main cause of intrinsic drug resistance in bacteria. Mycobacterium multidrug resistant (MMR) protein belongs to small multidrug resistant family proteins (SMR), causing multidrug resistance to proton (H(+))-linked lipophilic cationic drug efflux across the cell membrane. In the present work, MMR is treated as a novel target to identify new molecular entities as inhibitors for drug resistance in Mycobacterium tuberculosis.

Pharmacophore mapping and in silico screening to identify new potent leads for A(2A) adenosine receptor as antagonists.

A(2A) adenosine receptor (AR) antagonists play an important role in neurodegenerative diseases like Parkinson's disease. A 3D-QSAR study of A(2A) AR antagonists, was taken up to design best pharmacophore model. The pharmacophoric features (ADHRR) containing a hydrogen bond acceptor (A), a hydrogen bond donor (D), a hydrophobic group (H) and two aromatic rings (R), is projected as the best predictive pharmacophore model.

Identification of novel selective antagonists for cyclin C by homology modeling and virtual screening.

Cancer is a global multidrug resistant calamity, demanding an urgent need to design a novel/potent anti cancer agent. CDK8, 3/cyclin C biosynthetic pathway plays a specific role in G(0)/G(1)/S phases of cell cycle. Cyclin C is identified as a potential anti cancer target candidate.

Study of interactions between Mycobacterium tuberculosis proteins: SigK and anti-SigK.

The development of novel antituberculosis therapeutic molecules is a global health concern. Complex gene expression in Mycobacterium tuberculosis is mediated mainly by various sigma factors. The SigK protein binds to RNA polymerase, facilitating the expression of genes encoding the antigenic proteins mpt70 and mpt83.