Thiadiazine thione derivatives as anti-leishmanial agents: synthesis, biological evaluation, structure activity relationship, ADMET, molecular docking and molecular dynamics simulation studies.

During last decades, 3,5-disubstituted-tetrahydro--thiadiazine-2-thione scaffold remains the center of interest due to their ease of preparation, diverse range substituents at N-3 and N-5 positions, and profound biological activities. In the current study, a series of 3,5-disubstituted-tetrahydro--thiadiazine-2-thiones were synthesized in good to excellent yield, and the structure of the compounds were confirmed by various spectroscopic techniques such as FTIR, H-NMR, C-NMR and Mass spectrometry, and finally evaluated against . Whereas, all the evaluated compounds (1-33), demonstrate potential leishmanicidal activities with IC values in the range of (1.

Pharmacophore-based virtual screening, molecular docking and molecular dynamics studies for the discovery of novel neuraminidase inhibitors.

The in silico evaluation of 27 p-aminosalicylic acid derivatives, also referred to as neuraminidase inhibitors was the focus of the current study. To search and predict new potential neuraminidase inhibitors, this study was based on the ligand-based pharmacophore modeling, 3D QSAR, molecular docking, ADMET and MD simulation studies. The data was generated from recently reported inhibitors and divided into two groups, one of these group has 17 compounds for training and the second group has 10 compounds for testing purpose.

The anti-melanogenic properties of Swietenia macrophylla king.

Fair flawless skin is the goal for some cultures and the development of irregular skin pigmentation is considered an indication of premature skin aging. Hence, there is a rising demand for skin whitening cosmetics. Thus, this research will be focusing on discovering the anti-pigmentation properties of Swietenia macrophylla seeds.

Virtual screening of bioactive anti-SARS-CoV natural products and identification of 3β,12-diacetoxyabieta-6,8,11,13-tetraene as a potential inhibitor of SARS-CoV-2 virus and its infection related pathways by MD simulation and network pharmacology.

Since the first prevalence of COVID-19 in 2019, it still remains the most devastating pandemic throughout the world. The current research aimed to find potential natural products to inhibit the novel coronavirus and associated infection by MD simulation and network pharmacology approach. Molecular docking was performed for 39 natural products having potent anti-SARS-CoV activity.

Anti-Inflammatory and Anti-Rheumatic Potential of Selective Plant Compounds by Targeting TLR-4/AP-1 Signaling: A Comprehensive Molecular Docking and Simulation Approaches.

Plants are an important source of drug development and numerous plant derived molecules have been used in clinical practice for the ailment of various diseases. The Toll-like receptor-4 (TLR-4) signaling pathway plays a crucial role in inflammation including rheumatoid arthritis. The TLR-4 binds with pro-inflammatory ligands such as lipopolysaccharide (LPS) to induce the downstream signaling mechanism such as nuclear factor κappa B (NF-κB) and mitogen activated protein kinases (MAPKs).

Whole exome sequencing identifies a novel compound heterozygous GFM1 variant underlying developmental delay, dystonia, polymicrogyria, and severe intellectual disability in a Pakhtun family.

Mitochondrial protein synthesis requires three elongation factors including EF-Tu (TUFM; OMIM 602389), EF-Ts (TSFM; OMIM 604723), and EF-G1 (GFM1; OMIM 606639). Pathogenic variants in any of these three members result in defective mitochondrial translation which can impart an oxidative phosphorylation (OXPHOS) deficiency. In this study, we investigated a consanguineous Pakhtun Pakistani family.

Cosmeceutical Therapy: Engaging the Repercussions of UVR Photoaging on the Skin's Circadian Rhythm.

Sunlight is an important factor in regulating the central circadian rhythm, including the modulation of our sleep/wake cycles. Sunlight had also been discovered to have a prominent influence on our skin's circadian rhythm. Overexposure or prolonged exposure to the sun can cause skin photodamage, such as the formation of irregular pigmentation, collagen degradation, DNA damage, and even skin cancer.

Biodistribution Study of Niosomes in Tumor-Implanted BALB/C Mice Using Scintigraphic Imaging.

The purpose of this work was to study the biodistribution of niosomes in tumor-implanted BALB/c mice using gamma scintigraphy. Niosomes were first formulated and characterized, then radiolabeled with Technetium-99 m (Tc). The biodistribution of 99mTc-labeled niosomes was evaluated in tumor-bearing mice through intravenous injection and imaged with gamma scintigraphy.

Is Curcumin the Answer to Future Chemotherapy Cocktail?

The rise in cancer cases in recent years is an alarming situation worldwide. Despite the tremendous research and invention of new cancer therapies, the clinical outcomes are not always reassuring. Cancer cells could develop several evasive mechanisms for their survivability and render therapeutic failure.

Prospect of Anterior Gradient 2 homodimer inhibition via repurposing FDA-approved drugs using structure-based virtual screening.

Anterior Gradient 2 (AGR2) has recently been reported as a tumor biomarker in various cancers, i.e., breast, prostate and lung cancer.

Counteracting the Ramifications of UVB Irradiation and Photoaging with King Seed.

In this day and age, the expectation of cosmetic products to effectively slow down skin photoaging is constantly increasing. However, the detrimental effects of UVB on the skin are not easy to tackle as UVB dysregulates a wide range of molecular changes on the cellular level. In our research, irradiated keratinocyte cells not only experienced a compromise in their redox system, but processes from RNA translation to protein synthesis and folding were also affected.

Combined docking methods and molecular dynamics to identify effective antiviral 2, 5-diaminobenzophenonederivatives against SARS-CoV-2.

The aim of this work is to contribute to the research in finding lead compounds for clinical use, to identify new drugs that target the SARS-CoV-2 virus main protease (Mpro). In this study, we used molecular docking strategies to analyze 2.5-diaminobenzophenone compounds against Malaria and to compare results with the Nelfinavir as a FDA-approved HIV-1 protease inhibitor recommended for the treatment of COVID-19.

Therapeutic propensities, phytochemical composition, and toxicological evaluation of Anagallis arvensis (L.): A wild edible medicinal food plant.

Anagallis arvensis (L.) is a wild edible food plant that has been used in folklore as a natural remedy for treating common ailments. This study aimed to explore the biochemical properties and toxicity of methanol (MeOH) and dichloromethane (DCM) extracts of A.

G protein-coupled estrogen receptor-1: homology modeling approaches and application in screening new GPER-1 modulators.

G protein-coupled receptors (GPCRs) belong to the largest family of protein targets comprising over 800 members in which at least 500 members are the therapeutic targets. Among the GPCRs, G protein-coupled estrogen receptor-1 (GPER-1) has shown to have the ability in estrogen signaling. As GPER-1 plays a critical role in several physiological responses, GPER-1 has been considered as a potential therapeutic target to treat estrogen-based cancers and other non-communicable diseases.

Natural bioactive compounds as a new source of promising G protein-coupled estrogen receptor (GPER) modulators: comprehensive approach.

Cancer ranks in second place among the cause of death worldwide. Cancer progress in multiple stages of carcinogenesis and metastasis programs through complex pathways. Sex hormones and their receptors are the major factors in promoting cancer progression.

Detrimental Effects of UVB on Retinal Pigment Epithelial Cells and Its Role in Age-Related Macular Degeneration.

Retinal pigment epithelial (RPE) cells are an essential part of the human eye because they not only mediate and control the transfer of fluids and solutes but also protect the retina against photooxidative damage and renew photoreceptor cells through phagocytosis. However, their function necessitates cumulative exposure to the sun resulting in UV damage, which may lead to the development of age-related macular degeneration (AMD). Several studies have shown that UVB induces direct DNA damage and oxidative stress in RPE cells by increasing ROS and dysregulating endogenous antioxidants.

HPLC-PDA Polyphenolic Quantification, UHPLC-MS Secondary Metabolite Composition, and In Vitro Enzyme Inhibition Potential of .

The plants of the genus are widely explored regarding nutritive and medicinal purposes. In this study, dichloromethane (DCM) and methanol (MeOH) extracts of (Choisy.) aerial and flower parts were analyzed for high-performance liquid chromatography with photodiode array detection (HPLC-PDA), ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) phytochemical composition, and enzyme inhibition potential against key enzymes involved in diabetes (α-amylase), skin problems (tyrosinase), and inflammatory disorders (lipoxygenase (LOX)).

Engineering of Naproxen Loaded Polymer Hybrid Enteric Microspheres for Modified Release Tablets: Development, Characterization, in silico Modelling and in vivo Evaluation.

Background: Naproxen (NP) is a non-steroidal anti-inflammatory drug with poor aqueous solubility and low oral bioavailability, which may lead to therapeutic failure. NP causes crucial GIT irritation, bleeding, and peptic and duodenal ulcers.

Purpose Of The Study: This study aimed to engineer and characterize polymer hybrid enteric microspheres using an integrated (experimental and molecular modelling) approach with further development to solid dosage form with modified drug release kinetics and improved bioavailability.

Multidirectional insights into the biochemical and toxicological properties of Bougainvillea glabra (Choisy.) aerial parts: A functional approach for bioactive compounds.

The current research work was conducted in order to probe into the biochemical and toxicological characterisation of methanol and dichloromethane (DCM) extracts of Bougainvillea glabra (Choisy.) aerial parts. Biological fingerprints were assessed for in vitro antioxidant, key enzyme inhibitory and cytotoxicity potential.

Characterization, optimization, and in vitro evaluation of Technetium-99m-labeled niosomes.

Background And Purpose: Niosomes are nonionic surfactant-based vesicles that exhibit certain unique features which make them favorable nanocarriers for sustained drug delivery in cancer therapy. Biodistribution studies are critical in assessing if a nanocarrier system has preferential accumulation in a tumor by enhanced permeability and retention effect. Radiolabeling of nanocarriers with radioisotopes such as Technetium-99m (Tc) will allow for the tracking of the nanocarrier noninvasively via nuclear imaging.

Sequential ligand- and structure-based virtual screening approach for the identification of potential G protein-coupled estrogen receptor-1 (GPER-1) modulators.

G protein-coupled estrogen receptor-1 (GPER-1) is a seven transmembrane receptor, responsible for mediating rapid estrogen signaling in many physiological responses in reproductive, nervous, endocrine, immune and cardiovascular systems. Due to unavailability of the crystal structure of GPER-1, we have performed sequential ligand-based virtual screening (LBVS) and structure-based screening (SBVS) to identify potential GPER-1 modulators. LBVS and SBVS approaches were validated retrospectively using the Receiver Operating Curve (ROC) plot and the early Enrichment Factor (EF).

Investigations into the therapeutic effects of aerial and stem parts of Buxus papillosa C.K. Schneid.: In vitro chemical, biological and toxicological perspectives.

In this study, different solvent extracts (methanol, dichloromethane and n-hexane) from aerial and stem parts of Buxus papillosa C.K. Schneid (Buxaceae) were investigated for a panoply of bioassays.

Phytochemical profiling, antioxidant, enzyme inhibition and cytotoxic potential of flowers.

In this study, phytochemical composition, antioxidant, enzyme inhibition and cytotoxic activities of methanol and dichloromethane (DCM) extracts of flowers were investigated. Methanol extract was found to have higher total bioactive contents and UHPLC-MS analysis of methanol extract revealed the presence of well-known phenolic and flavonoid compounds. Antioxidant activities were performed by radical scavenging (DPPH and ABTS), reducing power (FRAP and CUPRAC), phosphomolybdenum (TAC) and metal chelating assays.

Biological, chemical and toxicological perspectives on aerial and roots of Filago germanica (L.) huds: Functional approaches for novel phyto-pharmaceuticals.

We investigated into the effects of methanol and dichloromethane extracts from aerial and roots of Filago germanica (L.) Huds (Astearaceae) on key enzymes (cholinesterases, α-glucosidase and urease), antioxidant capabilities, cytotoxic potential and secondary metabolomics profile. Total phenolic and flavonoids were determined by spectrophotometric technique and secondary metabolites composition by UHPLC-MS.