Identification of DprE1 inhibitors for tuberculosis through integrated in-silico approaches.

Decaprenylphosphoryl-β-D-ribose-2'-epimerase (DprE1), a crucial enzyme in the process of arabinogalactan and lipoarabinomannan biosynthesis, has become the target of choice for anti-TB drug discovery in the recent past. The current study aims to find the potential DprE1 inhibitors through in-silico approaches. Here, we built the pharmacophore and 3D-QSAR model using the reported 40 azaindole derivatives of DprE1 inhibitors.

An drug repurposing approach to identify HDAC1 inhibitors against glioblastoma.

Despite considerable improvement in therapy and diagnosis, brain tumors remain a global public health concern. Among all brain tumors, 80% are due to Glioblastoma. The average survival rate of a patient once diagnosed with glioblastoma is 15 months.

Design of PI3K-mTOR Dual Inhibitors for Ovarian Cancer: Are We on the Right Track?

Ovarian cancer is one of the most familiar kinds of gynecological cancer seen in women. Though it is not as familiar as breast cancer, the survival rate for ovarian cancer is very low when compared with breast cancer. Even after being one among the familiar types, to date, there are no proper treatments available for ovarian cancer.

Structure-activity relationship mediated molecular insights of DprE1 inhibitors: A Comprehensive Review.

Emerging threats of multi-drug resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) tuberculosis led to the discovery of a novel target which was entitled Decaprenylphosphoryl-β-D-ribose 2'-epimerase (DprE1) enzyme. DprE1 is composed of two isoforms, decaprenylphosphoryl-β-D-ribose oxidase (DprE1) and decaprenylphosphoryl-D-2-keto erythro pentose reductase (DprE2). The enzymes, DprE1 and DprE2, regulate the two-step epimerization process to form DPA (Decaprenylphosphoryl arabinose) from DPX (Decaprenylphosphoryl-D-ribose), which is the sole precursor in the cell wall synthesis of arabinogalactan (AG) and lipoarabinomannan (LAM).

Identification of potential Akt activators: a ligand and structure-based computational approach.

The Akt pathway plays a significant role in various diseases like Alzheimer's, Parkinson's, and Diabetes. Akt is the central protein whose phosphorylation controls many downstream pathways. Binding of small molecules to the PH domain of Akt facilitates its phosphorylation in the cytoplasm and upregulates the Akt pathway.

Computational design of a broad-spectrum multi-epitope vaccine candidate against seven strains of human coronaviruses.

Unlabelled: Spike (S) proteins are an attractive target as it mediates the binding of the SARS-CoV-2 to the host through ACE-2 receptors. We hypothesize that the screening of the S protein sequences of all the seven known HCoVs would result in the identification of potential multi-epitope vaccine candidates capable of conferring immunity against various HCoVs. In the present study, several machine learning-based tools were employed to design a broad-spectrum multi-epitope vaccine candidate targeting the S protein of seven known strains of human coronaviruses.

A Recent Appraisal of Artificial Intelligence and In Silico ADMET Prediction in the Early Stages of Drug Discovery.

In silico ADMET models have progressed significantly over the past ~4 decades, but still, the pharmaceutical industry is vexed by the late-stage toxicity failure of lead molecules. This problem of late-stage attrition of the drug candidates because of adverse ADMET profile motivated us to analyze the current role and status of different in silico tools along with the rise of machine learning (ML) based program for ADMET prediction. In this review, we have differentiated AI from traditional in silico tools because, unlike traditional in silico tools where the final decision is made manually, AI automates the decision-making prerogative of humans.

Computer-aided identification of human carbonic anhydrase isoenzyme VII inhibitors as potential antiepileptic agents.

Human carbonic anhydrase (hCA) belongs to a superfamily of metalloenzymes that reversibly catalyse the hydration of carbon dioxide to give bicarbonate (HCO) and proton (H). As HCO ions play an important role in neuronal signalling hence, hCA enzymes are an attractive target for antiepileptic drugs. Out of all the isoforms, hCA VII is predominantly expressed in the brain cortex and hippocampus region, which are the most affected area during seizure activity.

Exploration of small-molecule entry disruptors for chikungunya virus by targeting matrix remodelling associated protein.

Background And Purpose: A genome-wide clustered regularly interspaced short palindromic repeats- associated protein 9-based screen has revealed that the cell adhesion molecule matrix remodelling associated protein 8 (Mxra8) acts as an entry mediator for many alphaviruses including chikungunya virus. The first X-ray crystal structure reported for Mxra8 a few months ago has a low-resolution of 3.49Å.

Repurposing of existing FDA approved drugs for Neprilysin inhibition: An study.

Neprilysin (NEP) is a neutral endopeptidase with diverse physiological roles in the body. NEP's role in degradation of diverse classes of peptides such as amyloid beta, natriuretic peptide, substance P, angiotensin, endothelins, etc., is associated with pathologies of alzheimer's, kidney and heart diseases, obesity, diabetes and certain malignancies.

Computational approaches in efflux pump inhibitors: current status and prospects.

Treatment of bacterial infections is currently threatened by the development of antibiotic resistance and a poor pipeline of new antibiotics. Efflux pumps (EPs) are an integral part of the defense machinery of bacteria, preventing the entry of molecules, such as antibiotics, into the intracellular environment and resulting in antibiotic resistance. Therefore, research has focused on the discovery of novel EP inhibitors (EPIs), such as PAβN, D13-9001, and MBX2319.

Is viral E6 oncoprotein a viable target? A critical analysis in the context of cervical cancer.

An understanding of the pathology of cervical cancer (CC) mediated by E6/E7 oncoproteins of high-risk human papillomavirus (HPV) was developed by late 80's. But if we look at the present scenario, not a single drug could be developed to inhibit these oncoproteins and in turn, be used specifically for the treatment of CC. The readers are advised not to presume the "viability of E6 protein" as mentioned in the title relates to just druggability of E6.

Pharmacophore-guided fragment-based design of novel mammalian target of rapamycin inhibitors: extra precision docking, fingerprint-based 2D and atom-based 3D-QSAR modelling.

Rapamycin and their derivatives known as rapalogs were the first-generation mTOR inhibitors which interacted with mTORC1 but not with the mTORC2 protein. Second-generation inhibitors could bind with both and showed excellent anti-proliferative activity. Our aim was to design novel mTOR inhibitors which could bind at both the allosteric and the kinase site.

Molecular dynamics guided insight, binding free energy calculations and pharmacophore-based virtual screening for the identification of potential VEGFR2 inhibitors.

Vascular endothelial growth factor-A (VEGF-A) is a crucial member of the Vascular endothelial growth factor (VEGF) family which mediates the metastasis of tumor by 'angiogenic switch'. Therefore, targeting a VEGF-A mediated VEGFR2 signaling pathway is the most promising approach to repress the angiogenesis of tumor cells. VEGFR2 inhibitors are two types: Type I and Type II.

A Review on Anticancer Potentials of Benzothiazole Derivatives.

Benzothiazole is an organic compound bearing a heterocyclic nucleus (thiazole) which imparts a broad spectrum of biological activities to it. The significant and potent activity of benzothiazole moiety influenced distinctively by nature and position of substitutions. This review summarizes the effect of various substituents in recent trends and approaches to design and develop novel benzothiazole derivatives for anticancer potential in different cell lines by interpreting the Structure- Activity Relationship (SAR) and mechanism of action of a wide range of derivatives.

Identification of potential tumour-associated carbonic anhydrase isozyme IX inhibitors: atom-based 3D-QSAR modelling, pharmacophore-based virtual screening and molecular docking studies.

Tumour hypoxia results in dramatic changes in the gene expression, proliferation and survival of tumour cells. The tumour cells shift towards anaerobic glycolysis which results in change of pH in their microenvironment. In response to this stress, over expression of carbonic anhydrase IX (CA IX) genes is observed in many solid tumours.

Potentials of Diphenyl Ether Scaffold as a Therapeutic Agent: A Review.

Diphenyl ethers (DPE) and its analogs have exhibited excellent potential for therapeutic and industrial applications. Since the 19th century, intensive research is perpetuating on the synthetic routes and biological properties of DPEs. Few well-known DPEs are Nimesulide, Fenclofenac, Triclosan, Sorafenib, MK-4965, and MK-1439 which have shown the potential of this moiety as a lead scaffold for different pharmacological properties.