Systematic Review and Meta-analysis Indicating Curcumin to Enhance the Synergistic Potential of Paclitaxel and Reduce Cell Viability, Tumor Volume, and Drug Resistance in Different Cancers.

Background: To treat diseases like cancer, conventional Paclitaxel (PTX)- based monotherapy treatment regimens are becoming less effective due to the development of resistance. In this aspect, the phytomolecule curcumin (Cur), having ethnopharmacological importance in traditional South Asian remedies, like Ayurveda and Chinese traditional medicine, has been studied as a promising chemo-sensitizing and synergistic partner of PTX.

Aim: This study aimed to evaluate the combined effect of PTX and Cur compared to PTX therapy alone in the in vitro and in vivo environments.

Identification and characterization of the in-vivo metabolites of the novel soluble epoxide hydrolase inhibitor EC5026 using liquid chromatography quadrupole time of flight mass spectrometry.

EC5026 is a novel soluble epoxide hydrolase inhibitor being developed clinically to treat neuropathic pain and inflammation. In the current study, we employed the LC-ESI-Q-TOF-MS/MS technique to identify four in-vivo phase-I metabolites of EC5026 in rat model, out of which three were found to be novel. The identified metabolites include aliphatic hydroxylation, di-hydroxylation, terminal desaturation, and carboxylation.

Machine Learning, Molecular Docking, and Dynamics-Based Computational Identification of Potential Inhibitors against Lung Cancer.

Lung cancer is the most prevalent cause of cancer deaths worldwide. However, its treatment faces a significant hurdle due to the development of resistance. Phytomolecules are an important source of new chemical entities due to their rich chemical diversity.

A systematic pipeline of protein structure selection for computer-aided drug discovery: A case study on T790M/L858R mutant EGFR structures.

Virtual screening (VS) is a routine method to evaluate chemical libraries for lead identification. Therefore, the selection of appropriate protein structures for VS is an essential prerequisite to identify true actives during docking. But the presence of several crystal structures of the same protein makes it difficult to select one or few structures rationally for screening.

Identification of Bile Acid-Derived Chemical Chaperone(s) Targeting E46K-Mutated Alpha-Synuclein Protein to Treat Parkinson's Disease: Molecular Modelling, Docking, ADME, and Simulation Studies.

Aggregated α-synuclein (α-syn) present inside small cytoplasmic inclusions in the substantia nigra region marks the major pathological hallmark of Parkinson's disease (PD) and makes it an attractive target for the drug development process. Certain small-molecule chaperones (such as DCA, UDCA, TUDCA) presented the ability to prevent misfolding and aggregation of α-syn as well as to disentangle mature α-syn amyloid fibrils. However, due to toxicity constraints, these small molecules could not be translated into clinical settings.

A pharmacokinetic study to correlate the hypoglycemic effect of phlorizin in rats: Identification of metabolites as inhibitors of sodium/glucose cotransporters.

Phlorizin (PRZ) is a natural product that belongs to a class of dihydrochalcones. The unique pharmacological property of PRZ is to block glucose absorption or reabsorption through specific and competitive inhibitors of the sodium/glucose cotransporters (SGLTs) in the intestine (SGLT1) and kidney (SGLT2). This results in glycosuria by inhibiting renal reabsorption of glucose and can be used as an adjuvant treatment for type 2 diabetes.

Meta-Analysis of 49 SNPs Covering 25,446 Cases and 41,106 Controls Identifies Polymorphisms in Hormone Regulation and DNA Repair Genes Associated with Increased Endometrial Cancer Risk.

Endometrial cancer (EC) is among the most common gynecological disorders globally. As single nucleotide polymorphisms (SNPs) play an important role in the causation of EC, therefore, a comprehensive meta-analysis of 49 SNPs covering 25,446 cases and 41,106 controls was performed to identify SNPs significantly associated with increased EC risk. PubMed was searched to identify case control studies and meta-analysis was performed to compute the pooled odds ratio (OR) at 95% confidence interval (CI).

In-Silico molecular screening of natural compounds as a potential therapeutic inhibitor for Methicillin-resistant Staphylococcus aureus inhibition.

Methicillin-resistant Staphylococcus aureus (MRSA) is a life-threatening superbug causing infectious diseases such as pneumonia, endocarditis, osteomyelitis, etc. Conventional antibiotics are ineffective against MRSA infections due to their resistance mechanism against the antibiotics. The Penicillin Binding Protein (PBP2a) inhibits the activity of antibiotics by hydrolyzing the β-lactam ring.

Recent advances in the area of plant-based anti-cancer drug discovery using computational approaches.

Phytocompounds are a well-established source of drug discovery due to their unique chemical and functional diversities. In the area of cancer therapeutics, several phytocompounds have been used till date to design and develop new drugs. One of the desired interests of pharmaceutical companies and researchers globally is that new anti-cancer leads are discovered, for which phytocompounds can be considered a valuable source.

Elucidation of Increased Cervical Cancer Risk Due to Polymorphisms in XRCC1 (R399Q and R194W), ERCC5 (D1104H), and NQO1 (P187S).

Genetic variations like single nucleotide polymorphisms (SNPs) are associated with cervical carcinogenesis. In this study, SNPs have been identified that contribute toward changes in the function and stability of the proteins and show association with cervical cancer. Initially, literature mining identified 114 protein-coding polymorphisms with population-based evidence in cervical cancer.

Prioritization and Meta-analysis of regulatory SNPs identified IL6, TGFB1, TLR9 and MMP7 as significantly associated with cervical cancer.

Cervical cancer is a leading women cancer globally with respect to both incidence and mortality. Its increased risk has been linked with HPV infection and genetic variations like single nucleotide polymorphisms (SNPs). Although, studies have been published which evaluates the effect of SNPs in a few candidate genes, however the role of number of regulatory SNPs (rSNPs) in cervical cancer is not available.

Computational identification of natural product inhibitors against EGFR double mutant (T790M/L858R) by integrating ADMET, machine learning, molecular docking and a dynamics approach.

Double mutated epidermal growth factor receptor is a clinically important target for addressing drug resistance in lung cancer treatment. Therefore, discovering new inhibitors against the T790M/L858R (TMLR) resistant mutation is ongoing globally. In the present study, nearly 150 000 molecules from various natural product libraries were screened by employing different ligand and structure-based techniques.

A comprehensive meta-analysis of non-coding polymorphisms associated with precancerous lesions and cervical cancer.

Objectives: To study the risk of polymorphisms present in the non-coding regions of genes related with cervical cancer.

Methods: The PubMed database was extensively searched using text-mining techniques to identify literature containing the association of single nucleotide polymorphisms and cervical cancer. Case-control studies published till June 2020 were considered for the meta-analysis if they fulfilled the selection criteria.

EGFRisopred: a machine learning-based classification model for identifying isoform-specific inhibitors against EGFR and HER2.

The EGFR kinase pathway is one of the most frequently activated signaling pathways in human cancers. EGFR and HER2 are the two significant members of this pathway, which are attractive drug targets of clinical relevance in lung and breast cancer. Therefore, identifying EGFR- and HER2-specific inhibitors is one of the important challenges in cancer drug discovery.

TMLRpred: A machine learning classification model to distinguish reversible EGFR double mutant inhibitors.

The EGFR is a clinically important therapeutic drug target in lung cancer. The first-generation tyrosine kinase inhibitors used in clinics are effective against L858R-mutated EGFR. However, relapse of the disease due to the presence of resistant mutation (T790M) makes these inhibitors ineffective.

Synthesis of metronidazole based thiazolidinone analogs as promising antiamoebic agents.

Metronidazole and its derivatives are widely used for the treatment of amoebiasis. However, metronidazole is considered as the standard drug but it has many side effects. The present study describes the synthesis of a series of metronidazole based thiazolidinone analogs via Knoevenagel condensation of 4-[2-(2-methyl-5-nitro-1H-imidazole-1-yl)ethoxy]benzaldehyde 1 with various thiazolidinone derivatives 2-14 to get the new scaffold (15-27) having better activity and lesser toxicity.

ADMET profiling of geographically diverse phytochemical using chemoinformatic tools.

Phytocompounds are important due to their uniqueness, however, only few reach the development phase due to their poor pharmacokinetics. Therefore, preassessing the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties is essential in drug discovery. Biologically diverse databases (Phytochemica, SerpentinaDB, SANCDB and NuBBE) covering the region of India, Brazil and South Africa were considered to predict the ADMET using chemoinformatic tools (Qikprop, pkCSM and DataWarrior).

Exploring structural features of EGFR-HER2 dual inhibitors as anti-cancer agents using G-QSAR approach.

Simultaneous inhibition of EGFR and HER2 by dual-targeting inhibitors is an established anti-cancer strategy. Therefore, a recent trend in drug discovery involves understanding the features of such dual inhibitors. In this study, three different G-QSAR models were developed corresponding to individual EGFR, HER2 and the dual-model for both receptors.

QSAR of clinically important EGFR mutant L858R/T790M pyridinylimidazole inhibitors.

EGFR is a well-established therapeutic target of clinical relevance in cancer. However, acquisition of secondary mutation (T790M) makes first-generation inhibitors ineffective. Therefore, to circumvent the problem of resistance, new T790M/L858R (TMLR) double mutant inhibitors are required.

Structure-activity Relationship Study on Therapeutically Relevant EGFR Double Mutant Inhibitors.

Background: EGFR is a clinically approved drug target in cancer. The first generation tyrosine kinase inhibitors targeting L858R mutated EGFR are routinely used to treat non-small cell lung cancer (NSCLC). However, the presence of a secondary mutation (T790M) tenders these inhibitors ineffective and thus results in the relapse of the disease.

Unraveling structural requirements of amino-pyrimidine T790M/L858R double mutant EGFR inhibitors: 2D and 3D QSAR study.

EGFR is an important drug target in cancer. However, the ineffectiveness of first generation inhibitors due to the occurrence of a secondary mutation (T790M) results in the relapse of the disease. Identification of reversible inhibitors against T790M/L858R double mutants (TMLR) thus is a foremost requirement.

Insight into structural requirements of antiamoebic flavonoids: 3D-QSAR and G-QSAR studies.

Plant-based flavonoids have been found to exhibit strong inhibitory capability against Entamoeba histolytica. So, various QSAR models have been developed to identify the critical features that are responsible for the potency of these molecules. 3D-QSAR analysis using k-nearest neighbour molecular field analysis via stepwise forward-backward variable selection method showed best results for both internal and external predictive ability of the model (i.

Pharmacokinetic profiling of anticancer phytocompounds using computational approach.

Introduction: Natural products exhibit diverse scaffolds and are considered as suitable candidates for development of leads. However, poor pharmacokinetics often acts as a hindrance during the drug discovery process.

Objective: With a view of exploring the absorption, distribution, metabolism, excretion and toxicity (ADMET) profile of plant-based anticancer compounds, open-access databases (NPACT, CancerHSP and TaxKB) were analysed to identify molecules having properties favourable for drug ability.

Lycopene Prevents Mitochondrial Dysfunction during d-Galactosamine/Lipopolysaccharide-Induced Fulminant Hepatic Failure in Albino Rats.

Functional perturbation of mitochondria is associated with fulminant hepatic failure (FHF). d-Galactosamine/lipopolysaccharide (d-GalN/LPS)-induced FHF is a renowned model to evaluate the efficacy of hepatoprotective agents. Lycopene is an antioxidant and phytonutrient from the carotenoid family.