Thymol and carvacrol derivatives as anticancer agents; synthesis, activity, and computational analysis of biological targets.

Various thymol and carvacrol derivatives have been synthesized to test the anticancer activity potential. Computational methods including network pharmacology and molecular docking approaches were utilized to identify and assess the potential biological targets relating to cancer. Amongst the synthesized derivatives the ethoxy-cyclohexyl analogues were consistently the most active against a panel of 10 different cancer cell lines covering a variety of origins.

Identification of Novel Antileishmanial Chemotypes By High-Throughput Virtual and In Vitro Screening.

Background: Leishmaniasis is a deadly protozoan parasitic disease and a significant health problem in underdeveloped and developing countries. The global spread of the parasite, coupled with the emergence of drug resistance and severe side effects associated with existing treatments, has necessitated the identification of new and potential drugs.

Objective: This study aimed to identify promising compounds for the treatment of leishmaniasis by targeting two essential enzymes of Leishmania donovani: trypanothione reductase (Try-R) and trypanothione synthetase (Try-S).

Exploring marine-derived bioactive compounds for dual inhibition of Pseudomonas aeruginosa LpxA and LpxD: integrated bioinformatics and cheminformatics approaches.

Pseudomonas aeruginosa can cause serious nosocomial infections. Targeting the biosynthesis of Lipid A, a major structural domain of lipopolysaccharide (LPS) in P. aeruginosa has emerged as a valuable strategy for developing novel therapeutic agents.

Flavonoids as potential KRAS inhibitors: DFT, molecular docking, molecular dynamics simulation and ADMET analyses.

KRAS mutations linked with cancer. Flavonoids were docked against KRAS G12C and G12D receptors. Abyssinone III, alpha naphthoflavone, beta naphthoflavone, abyssinone I, abyssinone II and beta naphthoflavone, genistin, daidzin showed good docking scores against KRAS G12C and G12D receptors, respectively.

Identification of new potent NLRP3 inhibitors by multi-level in-silico approaches.

Nod-like receptor protein 3 (NLRP-3), is an intracellular sensor that is involved in inflammasome activation, and the aberrant expression of NLRP3 is responsible for diabetes mellitus, its complications, and many other inflammatory diseases. NLRP3 is considered a promising drug target for novel drug design. Here, a pharmacophore model was generated from the most potent inhibitor, and its validation was performed by the Gunner-Henry scoring method.

Prospective virtual screening combined with bio-molecular simulation enabled identification of new inhibitors for the KRAS drug target.

Lung cancer is a disease with a high mortality rate and it is the number one cause of cancer death globally. Approximately 12-14% of non-small cell lung cancers are caused by mutations in KRAS. The KRAS is one of the most prevalent mutants in lung cancer patients.

A hierarchical approach towards identification of novel inhibitors against L, D-transpeptidase YcbB as an anti-bacterial therapeutic target.

The bacterial cell wall, being a vital component for cell viability, is regarded as a promising drug target. The L, D-Transpeptidase YcbB enzyme has been implicated for a significant role in cell wall polymers cross linking during typhoid toxin release, β-lactam resistance and outer membrane defect rescue. These observations have been recorded in different bacterial pathogens such as , , and .

and evaluation of antifungal bioactive compounds from sp. strain 130 against .

spp. are considered excellent reservoirs of natural bioactive compounds. The study evaluated the bioactive potential of secondary metabolites from sp.

Network pharmacology and molecular dynamic simulation integrated strategy for the screening of active components and mechanisms of phytochemicals from on Alzheimer and cognitive decline.

Alzheimer's disease (AD) ranks as the most prevalent neurodegenerative disorder with dementia and it accounts for more than 70% of all cases. Despite extensive reporting on the experimental investigation of (DI) and its phytochemical components in the treatment of AD, the urgent need for elucidation of the principle of multi-mechanism and multi-level treatment of AD remains. In this research, molecular docking and network pharmacology were used to evaluate active compounds and molecular targets of DI for the treatment of AD.

Structural and Dynamical Basis of VP35-RBD Inhibition by Marine Fungi Compounds to Combat Marburg Virus Infection.

The Marburg virus (MBV), a deadly pathogen, poses a serious threat to world health due to the lack of effective treatments, calling for an immediate search for targeted and efficient treatments. In this study, we focused on compounds originating from marine fungi in order to identify possible inhibitory compounds against the Marburg virus (MBV) VP35-RNA binding domain (VP35-RBD) using a computational approach. We started with a virtual screening procedure using the Lipinski filter as a guide.

Identification of novel inhibitors against VP40 protein of Marburg virus by integrating molecular modeling and dynamics approaches.

Marburg virus (MV) is a highly etiological agent of haemorrhagic fever in humans and has spread across the world. Its outbreaks caused a 23-90% human death rate. However, there are currently no authorized preventive or curative measures yet.

Identification of novel STAT3 inhibitors for liver fibrosis, using pharmacophore-based virtual screening, molecular docking, and biomolecular dynamics simulations.

The signal transducer and activator of transcription 3 (STAT3) plays a fundamental role in the growth and regulation of cellular life. Activation and over-expression of STAT3 have been implicated in many cancers including solid blood tumors and other diseases such as liver fibrosis and rheumatoid arthritis. Therefore, STAT3 inhibitors are be coming a growing and interesting area of pharmacological research.

Network pharmacology based virtual screening of Flavonoids from and the molecular mechanism against inflammation.

Inflammation is a nonspecific immune response against injury caused by a harmful agent that strives to restore tissue function and homeostasis. L.f.

Investigating the role of Sterol C24-Methyl transferase mutation on drug resistance in leishmaniasis and identifying potential inhibitors.

Leishmaniasis is a fatal disease caused by the parasite. For the survival of the parasite, Sterol C24-Methyl Transferase (SMT) is essential which is an enzyme of the ergosterol pathway. SMT protein mutation is responsible for Amphotericin-B drug resistance in Leishmania, which is the main treatment for visceral leishmaniasis.

Synthesis and Anticancer Evaluation of 4-Chloro-2-((5-aryl-1,3,4-oxadiazol-2-yl)amino)phenol Analogues: An Insight into Experimental and Theoretical Studies.

We report herein the synthesis, docking studies and biological evaluation of a series of new 4-chloro-2-((5-aryl-1,3,4-oxadiazol-2-yl)amino)phenol analogues (). The new compounds were designed based on the oxadiazole-linked aryl core of tubulin inhibitors of IMC-038525 and IMC-094332, prepared in five steps and further characterized via spectral analyses. The anticancer activity of the compounds was assessed against several cancer cell lines belonging to nine different panels as per National Cancer Institute (NCI US) protocol.

Design, Synthesis, ADME, and Anticancer Studies of Newer -Aryl-5-(3,4,5-Trifluorophenyl)-1,3,4-Oxadiazol-2-Amines: An Insight into Experimental and Theoretical Investigations.

In continuance of our investigation into the anticancer activity of oxadiazoles, we report here the preparation of 10 new 1,3,4-oxadiazole analogues using the scaffold hopping technique. We have prepared the oxadiazoles having a common pharmacophoric structure (oxadiazole linked aryl nucleus) as seen in the reported anticancer agents IMC-038525 (tubulin inhibitor), IMC-094332 (tubulin inhibitor), and FATB (isosteric replacement of the S of thiadiazole with the O of oxadiazole). All of the oxadiazole analogues were predicted for their absorption, distribution, metabolism, and excretion (ADME) profiles and toxicity studies.

Establishing the Role of Iridoids as Potential Kirsten Rat Sarcoma Viral Oncogene Homolog G12C Inhibitors Using Molecular Docking; Molecular Docking Simulation; Molecular Mechanics Poisson-Boltzmann Surface Area; Frontier Molecular Orbital Theory; Molecular Electrostatic Potential; and Absorption, Distribution, Metabolism, Excretion, and Toxicity Analysis.

The RAS gene family is one of the most frequently mutated oncogenes in human cancers. In KRAS, mutations of G12D and G12C are common. Here, 52 iridoids were selected and docked against 8AFB (KRAS G12C receptor) using Sotorasib as the standard.

Development of a candidate multi-epitope vaccine against : Reverse vaccinology and immunoinformatics approach.

Objectives: To develop a candidate vaccine aginst the .

Methods: Since there is currently no vaccine against this pathogen, we employed in-silico methods to extensively explore the outer membrane toxin-producing proteins found specifically in to forecast a multi-epitope chimeric vaccine design. This computational study was conducted in Saudi Arabia in 2022 (study design: computational; ethical approval not applicable).

Bioinformatics and network pharmacology-based study to elucidate the multi-target pharmacological mechanism of the indigenous plants of Medina valley in treating HCV-related hepatocellular carcinoma.

The incidence of Hepatocellular Carcinoma (HCC) in Saudi Arabia is not surprising given the relatively high prevalence of hepatitis C virus (HCV) infection. Hepatitis C is also common in Saudi Arabia with a prevalence rate of 1% to 3% of the population, which further increases the risk of HCC. The incidence of HCC has been increasing in recent years, with HCV-related HCC accounting for a significant proportion of cases.

Resveratrol-Loaded Chia Seed Oil-Based Nanogel as an Anti-Inflammatory in Adjuvant-Induced Arthritis.

Natural anti-inflammatory nutraceuticals may be useful in preventing rheumatoid arthritis from worsening. Resveratrol (RV) and chia seed oil, having antioxidant potential, can assist in avoiding oxidative stress-related disorders. This investigation developed and evaluated resveratrol-loaded chia seed oil-based nanoemulsion (NE) gel formulations through in vitro and in vivo studies.

Discovery of potential phytochemicals as inhibitors of TcdB, a major virulence factors of .

is a gram-positive bacterium which is associated with different gastrointestinal related infections, and the numbers of cases related to it are continuously increasing in the past few years. Owing to high prevalence and development of resistance towards available antibiotics, it is required to develop new therapeutics to combat infection. The current study was aimed to identify novel phytochemicals that could bind and inhibits the TcdB, an exotoxin which is required for the pathogenesis of bacteria, and hence can be considered as the future drug candidates against .

HPLC Method Validation for the Estimation of Lignocaine HCl, Ketoprofen and Hydrocortisone: Greenness Analysis Using AGREE Score.

In the current study, the reversed-phased high-pressure liquid chromatography (RP-HPLC) method was proposed for the estimation of lignocaine hydrochloride (LIG), hydrocortisone (HYD) and Ketoprofen (KET) according to International Conference for Harmonization (ICH) Q2 R1 guidelines, in a gel formulation. The chromatographic evaluation was executed using Shimadzu RP-HPLC, equipped with a C8 column and detected using UV at 254 nm wavelength, using acetonitrile and buffer (50:50) as a mobile phase and diluent, at flow rate 1 mL/min and n injection volume of 20 μL. The retention time for LIG, HYD, and KET were 1.

Development and optimization of transethosomal gel of apigenin for topical delivery: In-vitro, ex-vivo and cell line assessment.

The main aim of this study was to optimize the transethosomes of apigenin formulated by the thin film hydration method using surfactant Span 80. Response surface Box-Behnken design with three levels of three factors was used to design and optimize the formulations. The prepared transethosomal formulations were characterized for entrapment efficiency, vesicle size, and flux to obtain the optimized formulation batch.

Screening of marine natural products for potential inhibitors targeting biotin biosynthesis pathway in .

Tuberculosis (TB) remains as one of the major public health concerns worldwide. A successful TB control and treatment is very challenging, due to continuing emergence of strains resistant to known drugs. Therefore, the development of new drugs with different chemical and biological approaches is necessary to obtain more efficient anti-tubercular therapeutics.

Molecular and Structural Analysis of Specific Mutations from Saudi Isolates of SARS-CoV-2 RNA-Dependent RNA Polymerase and their Implications on Protein Structure and Drug-Protein Binding.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has stressed the global health system to a significant level, which has not only resulted in high morbidity and mortality but also poses a threat for future pandemics. This situation warrants efforts to develop novel therapeutics to manage SARS-CoV-2 in specific and other emerging viruses in general. This study focuses on SARS-CoV2 RNA-dependent RNA polymerase (RdRp) mutations collected from Saudi Arabia and their impact on protein structure and function.