Strategies in synthetic design and structure-activity relationship studies of novel heterocyclic scaffolds as aldose reductase-2 inhibitors.

Heterocyclic scaffolds of natural as well as synthetic origin provide almost all categories of drugs exhibiting a wide range of pharmacological activities, such as antibiotics, antidiabetic and anticancer agents, and so on. Under normal homeostasis, aldose reductase 2 (ALR2) regulates vital metabolic functions; however, in pathological conditions like diabetes, ALR2 is unable to function and leads to secondary diabetic complications. ALR2 inhibitors are a novel target for the treatment of retinopathy (cataract) influenced by diabetes.

Benzimidazole-linked pyrazolo[1,5-a]pyrimidine conjugates: synthesis and detail evaluation as potential anticancer agents.

A library of benzimidazole briged pyrazolo[1,5-a]pyrimidine (6a-q) was designed, synthesized and subjected for evaluation for cytotoxic potential. Antiproliferative activity, ranging from 3.1-51.

COVID-19: Vaccines and therapeutics.

Coronavirus disease 2019 (COVID-19) is a communicable disease triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as leading cause of death from a single infectious agent globally. Despite of rigorous protective measures, availability of multiple vaccines and with few approved therapeutics, the virus effect on the humankind throughout the world is perennial. COVID-19 has become the most urgent health concern with emergence of new challenging variants which outnumbered all other health issues and ensued in overwhelming number of reported deaths.

Anti-PCSK9 monoclonal antibody attenuates high-fat diet and zymosan-induced vascular inflammation in C57BL/6 mice by modulating TLR2/NF-ƙB signaling pathway.

Objectives: Excess intake of a high-fatty diet (HFD) together with zymosan administration mediates vasculitis response which leads to impaired serum lipid levels and causes arterial stiffness. In the development of new cholesterol-lowering medications, PCSK9 inhibitor (proprotein convertase subtilisin/kexin type 9) is an emerging therapeutic. The goal of the present study was to see whether anti-PCSK9 mAb1 might prevent vasculitis in C57BL/6 mice by blocking TLR2/NF-B activation in HFD and Zymosan-induced vasculitis.

D-pinitol attenuates isoproterenol-induced myocardial infarction by alleviating cardiac inflammation, oxidative stress and ultrastructural changes in Swiss albino mice.

Cardiovascular diseases are the most disturbing problems throughout the world. The side effects of existing drugs are continuously compelling the scientist to look for better options in terms of safety, efficacy and cost-effectiveness. Our study is also a move in this direction.

Design, synthesis, in vitro antiproliferative evaluation and GSK-3β kinase inhibition of a new series of pyrimidin-4-one based amide conjugates.

A new series of novel amide conjugates of pyrimidin-4-one and aromatic/heteroaromatic /secondary cyclic amines has been synthesized and their in vitro antiproliferative activities against a panel of 60 human cancer cell lines of nine different cancer types were tested at NCI. Among the synthesized compounds, compound (4i) showed significant anti-proliferative activity. Compound (4i) displayed most potent activity against the breast tumor cell line T-47D and CNS tumor cell line SNB-75 exhibiting a growth of 1.

Stereoselective synthesis of ()-1,3-bis(α,β-unsaturated carbonyl)-isoindolines from aldehydes and phenacyl azides under metal free conditions.

Here in the present manuscript, we report our observation of an unprecedented stereoselective synthesis of 2-isoindolin-1,3-ylidenes from 2-(formylphenyl)acrylates and phenacylazide in the presence of piperidine. Unlike in our previous findings, in which we accessed 3-keto-isoquinolines from the same starting materials under slightly modified reaction conditions, this unexpected one-pot tandem reaction allows an efficient and simple method to access a variety of highly functionalized ethyl ()-2-(()-3-(2-oxo-2-arylethylidene)-2,3-dihydro-1-benzo[]isoindol-1-ylidene)-acetates in very good to excellent yields (up to 91%). The present methodology is compatible with a wide variety of functional groups.

Advances in 2-substituted benzothiazole scaffold-based chemotherapeutic agents.

Targeted therapy plays a pivotal role in cancer therapeutics by countering the drawbacks of conventional treatment like adverse events and drug resistance. Over the last decade, heterocyclic derivatives have received considerable attention as cytotoxic agents by modulating various signaling pathways. Benzothiazole is an important heterocyclic scaffold that has been explored for its therapeutic potential.

Exemestane encapsulated polymer-lipid hybrid nanoparticles for improved efficacy against breast cancer: optimization,characterization and cell culture studies.

Polymer-lipid hybrid nanoparticles (PLHNPs) are novel nanoplatforms for the effective delivery of a lipophilic drug in the management of a variety of solid tumors. The present work was designed to develop exemestane (EXE) encapsulated D-alpha-tocopheryl polyethylene glycol succinate (TPGS) based PLHNPs (EXE-TPGS-PLHNPs) for controlled delivery of EXE for breast cancer management. EXE-TPGS-PLHNPs were formulated by single-step nano-precipitation technique and statistically optimized by a 3Box-Behnken design using Design expertsoftware.

Synthesis, Molecular Docking, and Biological Evaluation of Some Novel 2- (5-Substituted 1,3,4-oxadiazole-2-yl)-1,3-benzothiazole Derivatives as Anticonvulsant Agents.

Background: Benzothiazole is an organosulfur heterocyclic compound that has a considerable place in drug discovery due to significant pharmacological actions.

Objective: The main objective of the present study was to synthesize some novel 2-(5-substituted 1,3,4-oxadiazole-2-yl)-1,3-benzothiazole derivatives and evaluate them for their anticonvulsant activity using in silico and in vivo methods.

Methods: A set of sixteen 2-(5-substituted 1, 3, 4-oxadiazole-2-yl)-1, 3-benzothiazole derivatives were prepared using multi-step reactions starting from o-amino-thiophenol and characterized by suitable spectral techniques.

3D printing technology in healthcare: applications, regulatory understanding, IP repository and clinical trial status.

Mass consumerization of three-dimensional (3D) printing innovation has revolutionised admittance of 3D-printing in an expansive scope of ventures. When utilised predominantly for industrial manufacturing, 3D-printing strategies have rapidly attained acquaintance in different parts of health care industry. 3D-printing is a moderately new technology that has discovered promising applications in the medication conveyance and clinical areas.

New indenopyrazole linked oxadiazole conjugates as anti-pancreatic cancer agents: Design, synthesis, in silico studies including 3D-QSAR analysis.

To continue the quest of newer anticancer agents, herein a novel class of 1,4-Dihydroindenopyrazole linked oxadiazole conjugates 9(a-r) was designed, synthesized and experimented for their anti-proliferative activities against four different cancer cell lines (human) such as MDA MB-231 (breast), PANC-1 (pancreatic), MCF-7 (breast), and Caco-2 (Colorectal) by using MTT assay. Among the series compound 9h and 9 m demonstrated significant potency against the PANC-1 (human pancreatic cancer cells) with IC value 7.4 μM and 4.

β-Carbolines as potential anticancer agents.

β-Carbolines are indole alkaloids having a tricyclic pyrido[3,4-b]indole ring in their structure. Since the isolation of first β-carboline from Peganum harmala in 1841, the isolation and synthesis of various β-carboline derivatives surged in the following centuries. β-Carboline derivatives due to their widespread availability from natural sources, structural flexibility, quick reactivity and interaction with varied anticancer targets such as DNA (intercalation, groove binding, etc.

Application of triazoles as bioisosteres and linkers in the development of microtubule targeting agents.

The triazole ring system has emerged as an exciting prospect in the optimization studies of promising lead molecules in the quest for new drugs for clinical usage. Several marketed drugs possess these versatile moieties that are used in a wide range of medical indications. This stems from the unique intrinsic properties of triazoles, which impart stability to the basic pharmacophoric unit with an added advantage of being a bioisostere of different chemical functionalities.

New imidazo[2,1-]thiazole-based aryl hydrazones: unravelling their synthesis and antiproliferative and apoptosis-inducing potential.

Herein, we have designed and synthesized new imidazo[2,1-]thiazole-based aryl hydrazones () and evaluated their anti-proliferative potential against a panel of human cancer cell lines. Among the synthesized compounds, and elicited promising cytotoxicity against the breast cancer cell line MDA-MB-231 with IC values of 1.65 and 1.

In-silico driven design and development of spirobenzimidazo-quinazolines as potential DNA gyrase inhibitors.

DNA gyrase and Topoisomerase IV are promising antibacterial drug targets as they regulate bacterial DNA replication and topology. In a quest for novel DNA topoisomerase inhibitors, a multidisciplinary approach was adopted that involves computational prediction of binding sites and molecular modelling followed by green synthesis and biological evaluation of antibacterial activity of spirobenzimidazo quinazolines derivatives. Using basic quantum chemistry principles, we evaluated spirobenzimidazo quinazolines derivatives with their pharmacokinetic profiles.

Liver X receptors and skeleton: Current state-of-knowledge.

The liver X receptors (LXR) is a nuclear receptor that acts as a prominent regulator of lipid homeostasis and inflammatory response. Its therapeutic effectiveness against various diseases like Alzheimer's disease and atherosclerosis has been investigated in detail. Emerging pieces of evidence now reveal that LXR is also a crucial modulator of bone remodeling.

Micro-RNAs in the regulation of immune response against SARS CoV-2 and other viral infections.

Background: Micro-RNAs (miRNAS) are non-coding, small RNAs that have essential roles in different biological processes through silencing genes, they consist of 18-24 nucleotide length RNA molecules. Recently, miRNAs have been viewed as important modulators of viral infections they can function as suppressors of gene expression by targeting cellular or viral RNAs during infection.

Aim Of Review: We describe the biological roles and effects of miRNAs on SARS-CoV-2 life-cycle and pathogenicity, and we discuss the modulation of the immune system with micro-RNAs which would serve as a new foundation for the treatment of SARS-CoV-2 and other viral infections.

Synthesis, biological evaluation, and molecular docking analysis of phenstatin based indole linked chalcones as anticancer agents and tubulin polymerization inhibitors.

A library of new phenstatin based indole linked chalcone compounds (9a-z and 9aa-ad) were designed and synthesized. Of these, compound 9a with 1-methyl, 2- and 3-methoxy substituents in the aromatic ring was efficacious against the human oral cancer cell line SCC-29B, spheroids, and in a mouse xenograft model of oral cancer AW13516. Compound 9a exhibited anti-cancer activity through disrupting cellular integrity and affecting glucose metabolism-which is a hallmark of cancer.

Base-mediated 1,3-dipolar cycloaddition of pyridinium bromides with bromoallyl sulfones: a facile access to indolizine scaffolds.

An expedient and transition-metal-free synthetic strategy has been developed for the construction of substituted indolizines from a unique combination of pyridinium salts and 2-bromoallyl sulfones. This approach does not compromise with the diverse substitutions on both the pyridinium salts and 2-bromoallyl sulfones. Wide substrate scope, operational simplicity, milder reaction conditions and good to moderate yields are the merits associated with the current approach.

Synthesis and biological evaluation of substituted N-(2-(1H-benzo[d]imidazol-2-yl)phenyl)cinnamides as tubulin polymerization inhibitors.

A new series of N-(2-(1H-benzo[d]imidazol-2-yl)phenyl) cinnamides was prepared and evaluated for their in vitro cytotoxic activity using various cancer cell lines viz. A549 (human non-small cell lung cancer), MDA-MB-231 (human triple negative breast cancer), B16-F10 (mouse melanoma), BT-474 (human breast cancer), and 4 T1 (mouse triple negative breast cancer). In the series of tested compounds, 12h showed potent cytotoxic activity against non-small cell lung cancer cell line with IC value of 0.

Embelin modulates metabolic endotoxemia and associated obesity in high fat diet fed C57BL/6 mice.

The present study was designed to investigate the effect of embelin in metabolic endotoxemia (ME) mediated inflammation and associated obesity in high fat diet (HFD)-fed C57BL/6 mice. The molecular docking of embelin confirms its binding with the toll-like receptor-4 (TLR-4). In vivo study, mice were treated with HFD for 8 weeks to induce ME mediated inflammation and associated obesity.

Synthesis and in Vitro Cytotoxicity Evaluation of Phenanthrene Linked 2,4- Thiazolidinediones as Potential Anticancer Agents.

Objective: To synthesize a series of phenanthrene-thiazolidinedione hybrids and explore their cytotoxic potential against human cancer cell lines of A-549 (lung cancer), HCT-116 and HT-29 (colon cancer), MDA MB-231 (triple-negative breast cancer), BT-474 (breast cancer) and (mouse melanoma) B16F10 cells.

Methods: A new series of phenanthrene-thiazolidinedione hybrids was synthesized via Knoevenagel condensation of phenanthrene-9-carbaldehyde and N-alkylated thiazolidinediones. The cytotoxicity (IC) of the synthesized compounds was determined by MTT assay.

Self assembly and hydrogelation of N-terminal modified tetrapeptide for sustained release and synergistic action of antibacterial drugs against methicillin resistant S. aureus.

Self assembly is a ubiquitous process of complex bio-molecules to perform various biological functions. This bottom-up approach applies in engineering of various nanostructures in different technological and biomedical applications. Here we report design and synthesis of phenolic acid conjugated tetra peptides which self assembled in uniform nanofibrils upon dissolution in aqueous solutions at physiological pH and formed stiff and transparent hydrogel.