Ravikumar Muttineni

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious and pathogenic virus. To date, there is a lack of proper medication against this virus, which has triggered the scientific community to find therapeutics. Searching of SARS-CoV-2 main protease inhibitors from anti-viral natural products based on traditional knowledg...

The outbreak of respiratory disease, COVID-19 caused by SARS-CoV-2 has now been spread globally and the number of new infections is rising every moment. There are no specific medications that are currently available to combat the disease. The spike receptor of SARS-CoV-2 facilitates the viral entry into a host cell and initiation of infection. Targ...

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is highly pathogenic to humans and has created an unprecedented global health care threat. Globally, intense efforts are going on to discover a vaccine or new drug molecules to control the COVID-19. However, till today, there is no effective therapeutics or treatment available for COVID-1...

Opioid analgesics are most commonly used analgesics in the treatment of chronic and severe pain. However these opioid analgesic compounds pose side effects such as respiratory depression psychological dependence etc. δ agonistic activity is associated with analgesic activity where as μ agonistic activity is associated with side effects. Hence, the...

Motivation. Inhibition of the p38 MAP kinase pathway has been shown to be beneficial in the treatment of inflammatory diseases. A three-dimensional quantitative structure-activity relationship (3D-QSAR) model, based on molecular field analysis (MFA), was developed for 41 urea derivatives that are inhibitors of p38 mitogen-activated protein kinase (...

A recent discovery of aromatase crystal structure triggered the efforts to design novel aromatase inhibitors for breast cancer therapy. While correlating docking scores with inhibitory potencies of known ligands, feeble robustness of scoring functions toward prediction was observed. This prompted us to develop new prediction models using stepwise r...

In recent years, there has been a growing interest in developing bacterial peptide deformylase (PDF) inhibitors as novel antibiotics. The purpose of the study is to generate a three-dimensional (3D) pharmacophore model by using diverse PDF inhibitors which is useful for designing of potential antibiotics. Twenty one structurally diverse compounds w...

Structure and ligand based pharmacophore modeling and docking studies carried out using diversified set of c-Jun N-terminal kinase-3 (JNK3) inhibitors are presented in this paper. Ligand based pharmacophore model (LBPM) was developed for 106 inhibitors of JNK3 using a training set of 21 compounds to reveal structural and chemical features necessary...

Anthranilic acid based derivatives (ANTs) have been identified as a novel class of potent tumor necrosis factor-α converting enzyme (TACE) inhibitors. A computational strategy based on molecular docking studies, followed by CoMFA and CoMSIA analyses has been performed to elucidate the atomic details of the TACE/ANT interactions and also to identify...

Bacillus anthracis is a causative organism of anthrax. The main reason to use anthrax as a bioweapon is the combination of the spore's durability and the lethal toxaemia of the vegetative stage. In anthrax infection, lethal factor (LF) is playing crucial role in causing cell death, by inhibiting pathways that rely on this kinase family. The combina...

c-Src kinase is a non receptor tyrosine kinase that acts as a signal transduction inhibitor, useful to treat various diseases, including cancer, osteoporosis, and metastatic bone disease. To discover novel high affinity ligands, Pharmacophore models were generated based upon a series of 29 structurally diverse chemicals exhibiting IC 50 values from...

Quantitative 3-D pharmacophore model was generated using 30 chemically diverse H3 receptor antagonists and tested for its productiveness using a large test set. It had 2 hydrogen bond acceptor lipids, 1 positive ionizable and 1 hydrophobic feature. Pharmacophore analysis suggested the structural features required for increased H3 receptor activity.

QSAR has been established for 73 Indole-carbaldehyde derivatives acting as Cannabinoid receptor 2 agonists. The best model was developed using six descriptors from topological, thermodynamic, spatial and electrotopological class. The model had r2 value of 0.888, PRESS value of 7.825, XV r2 value of 0.841 and test set correlation value 0.881.

Quantitative 3-D pharmacophore model was generated using 30 chemically diverse H3 receptor antagonists and tested for its productiveness using a large test set. It had 2 hydrogen bond acceptor lipids, 1 positive ionizable and 1 hydrophobic feature. Pharmacophore analysis suggested the structural features required for increased H3 receptor activity.

Traditionally, scientists identify new corrosion inhibitor molecules either by fiddling with existing inhibitors or by testing hundreds of compounds in a laboratory, which is a laborious, expensive and time-consuming process. Thus it became necessary to develop new inhibitors, which behave like corrosion inhibitors in less time, by In-silico approa...

The fundamental role that receptor tyrosine kinases play in cancer and other proliferative diseases has provided the impetus for an extensive effort to develop multikinase inhibitors. In this study three dimensional Pharmacophore models were developed using recently synthesized KDR and Tie-2 receptor tyrosine kinase inhibitors by using CATALYST Hyp...

Three Dimensional Pharmacophore model was developed based on 24 currently available c-Kit inhibitors. The best pharmacophore model (Hypo1) consists of four features namely one hydrogen bond acceptor, one hydrophobic point and two ring aromatics. The correlation coefficient, root mean square deviation and cost difference were 0.973, 0.729 and 100.98...

Caspase-3 belonging to a family of cysteine proteases is main executioner of apoptotic cascade pathway. The inhibitors of this protein are useful in the treatment of cardiomyopathy and neurodegenerative diseases. For the discovery of novel Caspase-3 non-peptide inhibitors from Maybridge database, ligand based and structure based virtual screening m...

c-Src kinase play an important role in cell growth and differentiation and its inhibitors can be useful for the treatment of various diseases, including cancer, osteoporosis, and metastatic bone disease. Three dimensional quantitative structure-activity relationship (3D-QSAR) studies were carried out on quinazolin derivatives inhibiting c-Src kinas...

A 3D QSAR analysis has been performed on a series of 67 benzodiazepine analogues reported as gamma-secretase inhibitors using molecular field analysis (MFA), with G/PLS to predict steric and electrostatic molecular field interaction for the activity. The MFA study was carried out using a training set of 54 compounds. The predictive ability of model...

MAPKAPK2, a substrate of p38 MAPKs, plays central role in p38-mediated signal transduction, and its inhibitors are promisingly useful in the treatment of inflammatory diseases. The computational approaches comprising both ligand-based drug design and structure-based drug design were used as virtual screening strategies for the discovery of novel MK...

This paper describes the generation of ligand-based as well as structure-based models and virtual screening of less toxic P-selectin receptor inhibitors. Ligand-based model, 3D-pharmacophore was generated using 27 quinoline salicylic acid compounds and is used to retrieve the actives of P-selectin. This model contains three hydrogen bond acceptors...

Adenosine receptor A2B (ADoR A2B) is an important G protein-coupled receptor (GPCR) of the rhodopsin family, and plays a pivotal role in gastrointestinal, neurological and hypersensitive disorders. QSAR and pharmacophore studies were carried out using 63 ADoR A2B inhibitor molecules to characterize molecular features and structural requirements for...

3D-QSAR analysis has been performed on a series of diaryl urea derivatives of multi-targeted receptor tyrosine kinase inhibitors. Models were developed using the most widely used computational approach molecular field analysis (MFA) from our dataset for the KDR, cKit and FLT3 inhibitors using genetic partial least square (G/PLS) method. These model...

Cathepsin K is a lysosomal cysteine protease that is highly and selectively expressed in osteoclasts, the cells which degrade bone during the continuous cycle of bone degradation and formation. Inhibition of cathepsin K represents a potential therapeutic approach for diseases characterized by excessive bone resorption such as osteoporosis. In order...

Motivation. Angiogenesis, the formation of new blood vessels from pre-existing vessels has been considered a critical event for growth and metastasis of solid tumors. KDR and Tie-2 are two receptor tyrosine kinases (RTK) that play primary role in tumor angiogenesis. Due to the vital role of RTK signaling in tumor progression, inhibition of RTK sign...

Aminoglycoside mimetics inhibit bacterial translation by interfering with the ribosomal decoding site. To elucidate the structural properties of these compounds important for antibacterial activity, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were applied to a set of 56 aminoglycosides...

With the objective to design new chemical entities with enhanced inhibitory potencies against p38 MAP alpha kinase, the 3D-QSAR and Comparative Molecular Field Analysis (CoMFA) studies were carried out on triazolopyridine oxazole compounds as inhibitors of these kinase is presented here. The developed model gave q(2) value of 0.707 and r(2) value o...

In the present study, a series of 179 quinoline and quinazoline heterocyclic analogues exhibiting inhibitory activity against Gastric (H+/K+)-ATPase were investigated using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices (CoMSIA) methods. Both the models exhibited good correlation between the calculated...

Consensus virtual screening models were generated and validated utilizing a set of known human epidermal growth factor receptor-2 (HER2) inhibitors and modeled HER2 active and inactive state structures. The virtual screening models were successfully employed to discover a set of structurally diverse compounds with growth inhibitory activity against...

Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed for 46 triazafluorenone derivatives, inhibiting metabotropic glutamate receptor subtype 1 (mGluR1). It includes molecular field analysis (MFA) and receptor surface analysis (RSA). The QSAR model was developed using 35 compounds and its predictive ability...

Mitogen-activated protein (MAP) p38 kinase is a serine-threonine protein kinase and its inhibitors are useful in the treatment of inflammatory diseases. Pharmacophore models were developed using HypoGen program of Catalyst with diverse classes of p38 MAP kinase inhibitors. The best pharmacophore hypothesis (Hypo1) with hydrogen-bond acceptor (HBA),...

Three-dimensional quantitative structure-activity relationship analysis of a set of 79 analogs of gamma-secretase inhibitors was performed by molecular field analysis with genetic partial least squares method to investigate the substitutional requirements to derive a predictive model and for the favorable receptor-drug interaction that may be used...

3D-QSAR analysis of a set of 37 analogues of SCH 66336 (Sarasar) was performed by most widely used computational tool, molecular field analysis (MFA) to investigate the substitutional requirements for the favorable receptor-drug interaction and to derive a predictive model that may be used for the designing of a novel farnesyltransferase inhibitors...

A 3D- QSAR model os Comparative Molecular Field Analysib (CoMFA) of 45 quinoline derivatives as metaborropic glutamate receptor subtype 1 (mGluR1) inhibitors wew investigated. The CoMFA analysis provided a model with q(2) value of 0.827 and r(2) value of 0.990, in which q(2) value of 0.827 and an r(2) value of 0.990, in which the good correlation b...

Motivation. The inhibition of farnesyltransferase (FTase) has been vigorously pursued as a promising target for the treatment of a broad spectrum of cancers. A set of hundred ether analogues reported as farnesyltransferase inhibitors (FTIs) were analyzed by employing the molecular field analysis (MFA) technique to investigate the structural require...

Protein farnesyltransferase (FTase) is a zinc-dependent enzyme that catalyzes the attachment of a farnesyl lipid group to the sulfur atom of a cysteine residue of numerous proteins involved in cell signaling including the oncogenic H-Ras protein. Pharmacophore models were developed by using Catalyst HypoGen program with a training set of 22 farnesy...

Leukotriene A4 hydrolase (LTA4H) is a hydrolase with a bifunctional zinc enzyme, which plays a role in inflammation. LTA4H may also play an important role in carcinogenesis, especially chronic inflammation-associated carcinogenesis. In this study, chemical feature based pharmacophore models based on 22 currently available LTA4H inhibitors have been...