Discovery of Furan-tethered Triazolothiadiazoles and Triazolothiadiazines as Potent Tyrosinase Inhibitors for the Treatment of Skin Diseases: Insights from Kinetics Data and Computational Modeling.

Introduction: Tyrosinase, a copper-containing enzyme, is responsible for melanin production, and its overactivity can lead to hyperpigmentation.

Methods: This study aimed to evaluate triazolothiadiazoles (3a-h, 4a-f) and triazolothiadiazines (5a-h) against human and mushroom tyrosinase isozymes.

Results: Several derivatives, such as 3a-3b, 3d, 4c-4f, 5d, and 5e, were identified as potent and selective inhibitors of mushroom tyrosinase, with IC50 values ranging from 1.

Identifying potent natural inhibitors of the hepatitis C virus NS3 protein using multiple computational and molecular approaches.

The NS3 protein of hepatitis C virus is an appealing target for therapeutic research because of its notable role in hepatitis C virus (HCV) replication and immune evasion. We employed a comprehensive interdisciplinary strategy to discover new inhibitors of the NS3 protein, targeting all major HCV genotypes (1a-6a) and mutant strains, using a combination of a structural-based drug design approach with in vitro and molecular studies. Initially, 14 potential binders were identified from our in-house database of approximately 950 compounds via docking-based screening.

Synthesis of (E)-3-(aryl)-1-phenylprop-2-en-1-one Chalcone Derivatives for Hyperglycemic Effect in Diabetes: In-vitro, In-vivo and In-silico Approach.

Background: Diabetes mellitus (DM) is a chronic metabolic disorder that seeks treatment instead of available mitigative therapy.

Methods: Six (E)-3-(aryl)-1-phenylprop-2-en-1-one chalcones were synthesized and characterized through various spectroscopic techniques. Their anti-diabetic potential was examined through in-vitro (α-glucosidase and α-amylase inhibition assays), in-vivo (alloxan-induced hyperglycemia), and in-silico studies.

Exploring tryptamine derivatives as potential agents for diabetes and cancer treatment: kinetics, molecular docking, and cell toxicity based investigations.

Abnormal glucose levels in diabetes mellitus cause chronic complications like neuropathy, nephropathy, retinopathy, cataract, and cardiovascular issues. Aldose reductase (AR), an enzyme in the polyol pathway, is crucial for developing treatments for diabetic complications. To this end, a series of twenty inhibitors based on tryptamine scaffolds were synthesized and assessed for their efficacy in inhibiting AR activity.

Semisynthesis of Novel Alicyclic Triterpene-Triazole Derivatives from Boswellia sacra Gum Resin: Potential Anti-breast Cancer and Immunomodulatory Effects on T‑Cell Activation.

In this current work, we report on the design, synthesis, cytotoxicity of new compounds, molecular docking studies, and and evaluations of 24 new alicyclic triterpene amide-containing 1-1,2,3-triazole derivatives (, , - and -). All new compounds were characterized by H-, C-, F-NMR, and HR-ESI-MS spectroscopic techniques. X-ray crystallography unambiguously confirmed the exact structure of .

Bioassay-guided isolation of a new cytotoxic compound targeting carbonic anhydrase-II: structure-activity relationships and dynamics studies.

Bioassay-guided isolation of A.J. Scott afforded one new natural product (lupeol butyl ether, ), along with sixteen known metabolites (-) reported from this source for the first time.

One-pot four-component synthesis of some novel hydrazone-Schiff bases of polyhydroquinoline as potent tyrosinase inhibitors: molecular docking and simulations approaches.

Seventeen novel polyhydroquinoline based Schiff bases were synthesized in excellent yields through Hantzsch reaction, characterized by means of spectroscopic techniques and finally screened for their tyrosinase inhibitory potential. Among the series, five compounds (IC = 8.93 ± 0.

Design and synthesis of terephthalic dihydrazide analogues as dual inhibitors of glycation and urease.

The overexpression of urease is the root cause of peptic ulcers and gastritis. Therefore, introducing new inhibitors against urease is a possible therapeutic approach to overcoming the pathogenesis; for instance, limiting the risk of development of urinary calculi. Moreover, glycation is the leading cause of several complications.

Two New α-Glucosidase Inhibitors from Haplophyllum tuberculatum: Inhibition Kinetics and Mechanistic Insights Through in Vitro and in Silico Approaches.

Diabetes is a multifactorial global health disorder marked by unusually high plasma glucose levels, which can lead to serious consequences including diabetic neuropathy, kidney damage, retinopathy, and cardiovascular disease. One effective therapy approach for reducing hyperglycemia associated with type 2 diabetes is to target α-glucosidase, enzymes that catalyze starch breakdown in the intestine. In the current study, two new (1, 2) and nine known (3-11) compounds were isolated from the rutaceous plant Haplophyllum tuberculatum and characterized by extensive nuclear magnetic resonance spectroscopic techniques and high-resolution electrospray ionization mass spectrometry.

Dihydrofolate reductase inhibitory potential of 1H-indole-based-meldrum linked 1H-1,2,3-triazoles as new anticancer derivatives: In-vitro and in-silico studies.

In this present work, we describe the syntheses of a new series of 32 1H-indole-based-meldrum linked 1H-1,2,3-triazole derivatives (2-13, 15a-15f, 16a-16f, 17a-17f and 19a, 19b, 20a), which constitute a new class of 1H-1,2,3-triazoles. Compounds 15a-15f, 16a-16f, 17a-17f have been prepared by employing "click" reactions between substituted 1H-indole-based meldrum alkynes (11, 12 and 13) and substituted aromatic azides (14a-14f) in the presence of copper iodide (CuI) and Hünig's base. Then, the synthesis of compounds 19, 20 through decomposition of meldrum moiety.

Contribution of mushroom farming to mitigating food scarcity: Current status, challenges and potential future prospects in Pakistan.

Food insecurity, pollution, and malnutrition are some critical issues tackled by the modern world in the recent era. However, edible mushrooms are nutritionally, economically, and biotechnologically valuable groups of macro fungi. Besides being an essential source of edible food, it is also exploited in pharmacological industries as a potential source of anticancer, antioxidant and immunomodulating agents.

In-silico and in-vitro studies to identify potential inhibitors of SARS-CoV-2 spike protein from Omani medicinal plants.

In the quest for novel therapeutic agents against SARS-CoV-2, the proposed study explores the potential of traditional Omani medicinal plants, focusing on the efficacy of natural ligands against the virus's Spike protein. Among 437 identified medicinal plants across Oman, 47 species that are documented for their traditional use in treating respiratory infections, with 30 species' ligands available were chosen for analysis. Molecular docking was performed using Autodock Vina on these ligands, yielding 406 unique ligands post-duplication removal.

Synthesis of 2,4-Bis(trifluoromethyl)benzaldehyde Hybrid Thiosemicarbazones as Prolyl Oligopeptidase Inhibitors for Neurodegenerative Disorders and their In-silico Analysis.

Introduction: Prolyl-specific oligopeptidase (POP), one of the brain's highly expressed enzymes, is an important target for the therapy of central nervous system disorders, notably autism spectrum disorder, schizophrenia, Parkinson's, Alzheimer's disease, and dementia.

Method: The current study was designed to investigate 2,4-bis(trifluoromethyl) benzaldehyde- based thiosemicarbazones as POP inhibitors to treat the above-mentioned disorders. A variety of techniques, such as nuclear magnetic resonance (NMR), mass spectrometry (MS), and Fourier-transform infrared spectroscopy (FTIR), were used for the structural confirmation of synthesized compounds.

Bioassay Guided Isolation and α-Glucosidase Inhibition Studies of a New Sesquiterpene from .

Aims: The aim of the current study was to explore the anti-diabetic potential of .

Methods: All the fractions of were evaluated for α-glucosidase inhibition, followed by bioassay-guided isolation which resulted in a new sesquiterpenoid, as a potential α-glucosidase inhibitor.

Results: The preliminary screening showed that all the fractions including -hexane (38.

Morpholine-tethered Novel Hydrazones as Promising Non-peptidic Prolyl Oligopeptidase (POP) Inhibitors: Synthesis In Vitro and In Silico Studies.

Introduction: Prolyl oligopeptidase (POP) is a pivotal druggable target implicated in diverse biological processes and linked to the development of various ailments, including neurodegenerative disorders. While conventional peptide-based inhibitors have been a centerpiece, their limitations, such as restricted bioavailability, necessitate exploration of non-peptidic inhibitors for their therapeutic potential.

Method: This study focuses on designing, synthesizing, and assessing morpholine-based hydrazones targeting the catalytic serine residue of POP.

Exploring the Therapeutic Potential of Coumarin-thiazolotriazole Pharmacophores for SARS-CoV-2 Spike Protein through and Evaluation.

Introduction: The pandemic caused by SARS-CoV-2 significantly impacted human life around the globe. Numerous unexpected modifications of the SARS-CoV-2 genome have resulted in the emergence of new types and have caused great concern globally.

Methods: Inhibitory effects of bioactive phytochemicals derived from natural and synthetic sources are promising for pathogenic viruses.

Synthesis of novel 1,2,3-triazole-tethered N-acyl hydrazones as a new class of carbonic anhydrase II inhibitors: In vitro and in silico potentials.

Carbonic anhydrase II (CA II) is crucial for maintaining homeostasis in several processes, including respiration, lipogenesis, gluconeogenesis, calcification, bone resorption, and electrolyte balance. It is a pivotal druggable target which is implicated in glaucoma, renal, gastric, and pancreatic carcinomas, as well as in malignant brain tumours. Therefore, to identify new CA II (bovine) inhibitors, the current study was designed to synthesize a library of 20 new triazole-linked hydrazones (6a-t).

Synthesis, and study of novel 1,3-diphenylurea derived Schiff bases as competitive α-glucosidase inhibitors.

Diabetes mellitus has become a major global health burden because of several related consequences, including heart disease, retinopathy, cataracts, metabolic syndrome, collapsed renal function, and blindness. In the recent study, thirty Schiff base derivatives of 1,3-diphenylurea were synthesized and their anti-diabetic activity was evaluated by targeting α-glucosidase. The compounds exhibited an overwhelming inhibitory potential for α-glucosidase with higher potency ranging from 2.

Corrigendum to "Antimicrobial topical polymeric films loaded with Acetyl-11-keto-β-boswellic acid (AKBA), boswellic acid and silver nanoparticles: Optimization, characterization, and biological activity" [Heliyon 10(11) 15th June 2024, e31671].

[This corrects the article DOI: 10.1016/j.heliyon.

Disrupting protease and deubiquitinase activities of SARS-CoV-2 papain-like protease by natural and synthetic products discovered through multiple computational and biochemical approaches.

The single-stranded RNA genome of SARS-CoV-2 encodes several structural and non-structural proteins, among which the papain-like protease (PLpro) is crucial for viral replication and immune evasion and has emerged as a promising therapeutic target. The current study aims to discover new inhibitors of PLpro that can simultaneously disrupt its protease and deubiquitinase activities. Using multiple computational approaches, six compounds (CP1-CP6) were selected from our in-house compounds database, with higher docking scores (-7.

Phytoconstituents with cardioprotective properties: A pharmacological overview on their efficacy against myocardial infarction.

Myocardial infarction (MI) is considered one of the most common cardiac diseases and major cause of death worldwide. The prevalence of MI and MI-associated mortality have been increasing in recent years due to poor lifestyle habits viz. residency, obesity, stress, and pollution.

Antimicrobial topical polymeric films loaded with Acetyl-11-keto-β-boswellic acid (AKBA), boswellic acid and silver nanoparticles: Optimization, characterization, and biological activity.

The study examined the antimicrobial and antioxidant potential of pure Acetyl-11-keto-β-boswellic acid (AKBA), boswellic acid (70%) and AKBA loaded nanoparticles as topical polymeric films. The optimized concentration (0.05 % w/v) of pure AKBA, boswellic acid (BA), and AKBA loaded silver nanoparticles were used to study its impact on film characteristics.

Identification of small molecular inhibitors of SIRT3 by computational and biochemical approaches a potential target of breast cancer.

Sirtuin 3 (SIRT3) belongs to the Sirtuin protein family, which consists of NAD-dependent lysine deacylase, involved in the regulation of various cellular activities. Dysregulation of SIRT3 activity has been linked to several types of cancer, including breast cancer. Because of its ability to stimulate adaptive metabolic pathways, it can aid in the survival and proliferation of breast cancer cells.