Flavin mononucleotide, a potent inhibitor of insulin-degrading enzyme: an study.

Diabetes Mellitus is a metabolic disorder which has affected over 476 million people globally with projections indicating a further increase in this number. Despite the availability of treatment therapies, maintaining optimal blood glucose levels remains a critical task. During literature survey, we came across Insulin degrading enzyme (IDE) which is responsible for insulin degradation in the body and inhibition of this enzyme could increase the bioavailability of insulin in the body.

Inhibition of Virulence Associated Traits by β-Sitosterol Isolated from Hibiscus rosa-sinensis Flowers Against Candida albicans: Mechanistic Insight and Molecular Docking Studies.

The emerging drug resistance and lack of safer and more potent antifungal agents make Candida infections another hot topic in the healthcare system. At the same time, the potential of plant products in developing novel antifungal drugs is also in the limelight. Considering these facts, we have investigated the different extracts of the flowers of Hibiscus rosa-sinensis of the Malvaceae family for their antifungal efficacy against five different pathogenic Candida strains.

Fluoroquinolones tackling antimicrobial resistance: Rational design, mechanistic insights and comparative analysis of norfloxacin vs ciprofloxacin derivatives.

Antimicrobial resistance poses a global health concern and develops a need to discover novel antimicrobial agents or targets to tackle this problem. Fluoroquinolone (FN), a DNA gyrase and topoisomerase IV inhibitor, has helped to conquer antimicrobial resistance as it provides flexibility to researchers to rationally modify its structure to increase potency and efficacy. This review provides insights into the rational modification of FNs, the causes of resistance to FNs, and the mechanism of action of FNs.

Coumarin as an Elite Scaffold in Anti-Breast Cancer Drug Development: Design Strategies, Mechanistic Insights, and Structure-Activity Relationships.

Breast cancer is the most common cancer among women. Currently, it poses a significant threat to the healthcare system due to the emerging resistance and toxicity of available drug candidates in clinical practice, thus generating an urgent need for the development of new potent and safer anti-breast cancer drug candidates. Coumarin (chromone-2-one) is an elite ring system widely distributed among natural products and possesses a broad range of pharmacological properties.

Antidiabetic potential of thiazolidinedione derivatives with efficient design, molecular docking, structural activity relationship, and biological activity: an update review (2021-2023).

Thiazolidinedione has been used successfully by medicinal chemists all over the world in the development of potent antidiabetic derivatives. The few compounds with excellent antidiabetic potency that we have identified in this review could be used as a lead for further research into additional antidiabetic mechanisms. The information provided in this review regarding the design, biological activity, structure-activity relationships, and docking studies may be useful for scientists who wish to further explore this scaffold in order to fully utilize its biological potential and develop antidiabetic agents that would overcome the limitations of currently available medications for the treatment of diabetes.

Triazole derivatives as potential xanthine oxidase inhibitors: Design, enzyme inhibition potential, and docking studies.

Considerable ingenuity has been shown in the recent years in the discovery of novel xanthine oxidase (XO) inhibitors that fall outside the purine scaffold. The triazole nucleus has been the cornerstone for the development of many enzyme inhibitors for the clinical management of several diseases, where hyperuricemia is one of them. Here, we give a critical overview of significant research on triazole-based XO inhibitors, with respect to their design, synthesis, inhibition potential, toxicity, and docking studies, done till now.

Pathology, target discovery, and the evolution of XO inhibitors from the first discovery to recent advances (2020-2023).

Hyperuricemia, a disease characterized by elevation of serum uric acid level beyond 6 mg/dL. This elevation led to appearance of symptoms from joint pain to gout and from gout to difficulty in mobility of the patient. So, in this review, we have summarized the pathology of hyperuricemia, discovery of target and discovery of first XO inhibitor.

Discovery of triazole tethered thymol/carvacrol-coumarin hybrids as new class of α-glucosidase inhibitors with potent in vivo antihyperglycemic activities.

Keeping in view the inhibitory potential of monoterpenes thymol and carvacrol as well as coumarin nucleus against α-glucosidase, novel series of thymol/carvacrol-coumarin hybrids was designed, synthesized and evaluated for α-glucosidase inhibitory potential. Among the series of hybrid molecules, AS14 with IC value of 4.32 ± 0.

Pathogenesis of Alzheimer's Disease and Diversity of 1,2,3-Triazole Scaffold in Drug Development: Design Strategies, Structural Insights, and Therapeutic Potential.

Alzheimer's disease is a most prevalent form of dementia all around the globe and currently poses a significant challenge to the healthcare system. Currently available drugs only slow the progression of this disease rather than provide proper containment. Identification of multiple targets responsible for this disease in the last three decades established it as a multifactorial neurodegenerative disorder that needs novel multifunctional agents for its management and the possible reason for the failure of currently available single target clinical drugs.

Mechanistic insight and structure activity relationship of isatin-based derivatives in development of anti-breast cancer agents.

Breast cancer is most common in women and most difficult to manage that causes highest mortality and morbidity among all diseases and posing significant threat to mankind as well as burden on healthcare system. In 2020, 2.3 million women were diagnosed with breast cancer and it was responsible for 685,000 deaths globally, suggesting the severity of this disease.

Shikonin derivatives as potent xanthine oxidase inhibitors: study.

Induction of hypersensitivity reactions (may be fatal too) by specific XO inhibitors has led to development of new molecules that are efficacious and have safer ADME profile. Among natural compounds, biologically active Alkannin/Shikonin (A/S) derivatives have unexplored XO inhibition potential. Therefore, their -hexenylnaphthazarin nucleus was studied and found that the nucleus is similar to that of allopurinol, signifying the XO inhibitory potential of these derivatives.

Quinoline derivatives volunteering against antimicrobial resistance: rational approaches, design strategies, structure activity relationship and mechanistic insights.

Emergence of antimicrobial resistance has become a great threat to human species as there is shortage of development of new antimicrobial agents. So, its mandatary to combat AMR by initiating research and developing new novel antimicrobial agents. Among phytoconstituents, Quinoline (nitrogen containing heterocyclic) have played a wide role in providing new bioactive molecules.

Dihydrofolate reductase inhibitors: patent landscape and phases of clinical development (2001-2021).

Introduction: Dihydrofolate reductase (DHFR) plays an important role in the biosynthesis of amino acid and folic acid. It participates by reducing dihydrofolate to tetrahydrofolate, in the presence of nicotinamide dinucleotide phosphate cofactor, and has been verified by various clinical studies to use DHFR as a target for the treatment of cancer and various bacterial infections.

Area Covered: In this review, we have disclosed patents of synthetics and natural DHFR inhibitors with diaminopyrimidine and quinazoline nucleus from 2001.

Evaluation of HPV E6/E7 mRNA Detection in Clinically Suspected Cases of Cervical Cancer with Abnormal Cytology: Time to Upgrade the Screening Protocols.

 Human papillomavirus (HPV) E6/E7 mRNA tests determine the oncogenic activity of the virus and represent a good clinical biomarker for predicting the risk of cervical cancer. So, the present study was conducted to know the role of HPV E6/E7 mRNA as a predictive biomarker for cervical carcinoma.  The present study was conducted on 55 clinical samples of cervical scrapings and biopsy from the clinically suspected cases (based on signs and symptoms) of cervical cancer having abnormal PAP smear.

Synthetic heterocyclic derivatives as promising xanthine oxidase inhibitors: An overview.

Inhibition of xanthine oxidase (XO) is an effective and most prominent therapeutic approach for the management of gout. Discovery of its association in the pathophysiology of diabetes, cardiovascular disorders, etc., widened its therapeutic horizons.

Design, synthesis, and biological evaluation of isatin-indole-3-carboxaldehyde hybrids as a new class of xanthine oxidase inhibitors.

A novel series of triazole-linked isatin-indole-3-carboxaldehyde hybrids based on the febuxostat skeleton and its binding site interactions were rationally designed and synthesized as potential xanthine oxidase inhibitors. Among the synthesized hybrids, A19 showed the most potent xanthine oxidase inhibition (IC  = 0.37 µM) with the mixed-type inhibitory scenario.

Donepezil-Inspired Multitargeting Indanone Derivatives as Effective Anti-Alzheimer's Agents.

In continuous efforts to develop anti-Alzheimer's agents, we rationally designed and synthesized a series of multitargeting molecules by incorporating the essential molecular features of the standard drug donepezil. Among the series, compound showed multitargeting properties to act as an anti-Alzheimer's agent, which is better tolerable in vivo than donepezil. Acetylcholinesterase (AChE) inhibition data showed that compound inhibits the enzyme with a half-maximal inhibitory concentration (IC) value of 0.

Discovery of potent inhibitors for M enzyme of SARS-COV2 by multi-stage in-silico screening of Alkannin/shikonin.

Novel coronavirus disease, a serious challenge for the healthcare system, has diverted all the researchers toward the exploration of potential targets, compounds or vaccines for the management of this disease. M enzyme was found to be crucial for replication of this virus which makes this enzyme an attractive drug target for SARS-CoV-2. Diverse pharmacological profile of Alkannin/shikonin (A/S) derivatives build up curiosity to study their antiviral profile.

Design, synthesis, and biological evaluation of novel morpholinated isatin-quinoline hybrids as potent anti-breast cancer agents.

Keeping in view the emerging need for potent and safer anti-breast cancer agents as well as the pharmacological attributes of isatin, quinolone, and morpholine derivatives, novel hydrazine-linked morpholinated isatin-quinoline hybrids were designed, synthesized, and evaluated as anti-breast cancer agents. The synthesized hybrid compounds were preliminarily screened against two breast cancer cell lines (MCF-7 and MDA-MB-231). Almost all synthetics showed potent inhibitory potential against hormone-positive MCF-7 cells while being inactive against hormone-negative MDA-MB-231 cells.

Most recent strategies targeting estrogen receptor alpha for the treatment of breast cancer.

Breast cancer is the most prominent, frequently diagnosed and leading cause of death among women. Estrogen is an agonist of estrogen receptor alpha (ER-α), expressed in mammary glands and is responsible for initiating many signalling pathways that lead to differentiation and development of breast tissue. Any mutations in these signalling pathways result in irregular growth of mammary tissue, leading to the development of tumour or cancer.

Xanthine oxidase inhibitors: patent landscape and clinical development (2015-2020).

Introduction: Xanthine oxidase (XO) is a molybdoflavoprotein that catalyzes the oxidative hydroxylation of purines to produce uric acid and reactive oxygen species. These reaction products can cause severe disease conditions like hyperuricemia which makes XO enzyme, an important therapeutic target in diseases like gout.

Areas Covered: Herein, patents from 2015 to 2020 are discussed to disclose the synthetic, as well as natural compounds, claimed to inhibit XO enzyme.

Rational approaches for the design of various GABA modulators and their clinical progression.

GABA (γ-amino butyric acid) is an important inhibitory neurotransmitter in the central nervous system. Attenuation of GABAergic neurotransmission plays an important role in the etiology of several neurological disorders including epilepsy, Alzheimer's disease, Huntington's chorea, migraine, Parkinson's disease, neuropathic pain, and depression. Increase in the GABAergic activity may be achieved through direct agonism at the GABA receptors, inhibition of enzymatic breakdown of GABA, or by inhibition of the GABA transport proteins (GATs).