Structure-based drug design of pre-clinical candidate nanopiperine: a direct target for CYP1A1 protein to mitigate hyperglycaemia and associated microbes.

Diabetes is attributed to an increased vulnerability to bacterial infection linked to unregulated hyperglycaemia. The present study highlights the formulation of nanoparticles with phyto-compound piperine (PIP) encapsulated within non-toxic biodegradable polymer poly-lactide co-glycolide (PLGA) which showed a variety in surface functionality, biocompatibility, and the ability to tailor an optimized release rate from its polymeric enclosure. The observations revealed that nanopiperine (NPIP) pre-treatment in mice inhibited alteration in hepatic tissue architecture and hepato-biochemical parameters in diabetes and its associated bacterial infections.

To quest new targets of parasite and their potential inhibitors to combat antimalarial drug resistance.

Malaria remains a global health challenge with significant mortality and morbidity annually, with resistant parasite strains complicating treatment efforts. There is an acute need for novel antimalarial drugs that can put a stop to the future public health crisis caused by the multi-drug resistance strains of the parasite However, the discovery of these new components is very challenging in the context of the generation of multi-drug resistance properties of malaria. The novel drugs also need to have several properties involving enhanced therapeutic prospects, successful treatment capabilities, and novel mechanisms of action that will forestall the resistance.

To Explore Potential Natural Inhibitors of Cysteine Proteases to Combat Human African Trypanosomiasis and Chagas Disease.

Background: Human African Trypanosomiasis (HAT), also known as sleeping sickness, and Chagas disease are neglected tropical diseases caused by Trypanosoma brucei and Trypanosoma cruzi, respectively. These diseases present significant challenges in treatment due to the toxicity, low efficacy, and drug-resistant strains associated with current therapies.

Introduction: Cysteine proteases play vital roles in the life cycles of these parasites, making them potential targets for therapeutic intervention.

Flavopiridol inhibits adipogenesis and improves metabolic homeostasis by ameliorating adipose tissue inflammation in a diet-induced obesity model.

Repositioning of FDA approved/clinical phase drugs has recently opened a new opportunity for rapid approval of drugs, as it shortens the overall process of drug discovery and development. In previous studies, we predicted the possibility of better activity profiles of flavopiridol, the FDA approved orphan drug with better fit value 2.79 using a common feature pharmacophore model for anti-adipogenic compounds (CFMPA).

Curcumin Mitigates Streptozotocin-Induced Genotoxicity In Vivo by Activating P53 Protein and Inhibiting Oxidative Stress and Chromosomal Aberration.

Background: Genotoxins are chemical constituents that damage DNA or chromosomal architecture, leading to alterations in the genetic level. Streptozotocin, a monofunctional nitrosourea derivative, is often utilized to induce diabetes mellitus in laboratory animals because of its detrimental effects on pancreatic cells. The purpose of this work was to investigate possible protective efficacy against the genotoxic effects of Streptozotocin.

To Explore Potential Inhibitors Against Various Enzymatic Targets of Human African Trypanosomiasis.

Synthetic drugs currently prescribed for the treatment of Human African Trypanosomiasis (HAT) are non-specific, toxic, demand extended therapeutic regimes and are of varying efficacy. Along with the challenging demographic and socio-economic hurdles, the everincreasing risk of drug resistance is another major problem to be addressed. Cysteine protease, Heat shock proteins (HSP-90), Trypanothione reductase (TR), Farnesyl diphosphate synthase, Glucose-6-phosphate dehydrogenase, UP-4-galactose epimerase, and Cytidine triphosphate synthetase are potential enzymatic targets for the development of novel inhibitors against HAT which are the main focus of this review.

Novel PLGA-encapsulated-nanopiperine promotes synergistic interaction of p53/PARP-1/Hsp90 axis to combat ALX-induced-hyperglycemia.

The present study predicts the molecular targets and druglike properties of the phyto-compound piperine (PIP) by in silico studies including molecular docking simulation, druglikeness prediction and ADME analysis for prospective therapeutic benefits against diabetic complications. PIP was encapsulated in biodegradable polymer poly-lactide-co-glycolide (PLGA) to form nanopiperine (NPIP) and their physico-chemical properties were characterized by AFM and DLS. ∼ 30 nm sized NPIP showed 86.

Enhanced Drug Carriage Efficiency of Curcumin-Loaded PLGA Nanoparticles in Combating Diabetic Nephropathy via Mitigation of Renal Apoptosis.

Objectives: The -derived diferuloylmethane compound CUR, loaded on Poly (lactide-co-glycolic) acid (PLGA) nanoparticles was utilized to combat DN-induced renal apoptosis by selectively targeting and modulating Bcl2.

Methods: Upon molecular docking and screening study CUR was selected as the core phytocompound for nanoparticle formulation. PLGA-nano-encapsulated-curcumin (NCUR) were synthesized following standard solvent displacement method.

To Investigate Growth Factor Receptor Targets and Generate Cancer Targeting Inhibitors.

Receptor tyrosine kinase (RTK) regulates multiple pathways, including Mitogenactivated protein kinases (MAPKs), PI3/AKT, JAK/STAT pathway, etc. which has a significant role in the progression and metastasis of tumor. As RTK activation regulates numerous essential bodily processes, including cell proliferation and division, RTK dysregulation has been identified in many types of cancers.

Exploring the Targets of Dengue Virus and Designs of Potential Inhibitors.

Background: Dengue, a mosquito-borne viral disease spread by the dengue virus (DENV), has become one of the most alarming health issues in the global scenario in recent days. The risk of infection by DENV is mostly high in tropical and subtropical areas of the world. The mortality rate of patients affected with DENV is ever-increasing, mainly due to a lack of anti-dengue viral-specific synthetic drug components.

Aromatic Plants as Potential Resources to Combat Osteoarthritis.

Osteoarthritis, which affects an estimated 10% of men and 18% of women over the age of 60 and is increasing in genetic prevalence and incidence, is acknowledged as the condition that degrades the quality of life for older adults in the world. There is currently no known treatment for osteoarthritis. The majority of therapeutic methods slow the progression of arthritis or treat its symptoms, making effective treatment to end the degenerative process of arthritis elusive.

Morroniside interaction with poly (ADP-ribose) polymerase accentuates metabolic mitigation of alloxan-induced genotoxicity and hyperglycaemia: a molecular docking based and experimental therapeutic insight.

The present study tends to evaluate the possible potential of bio-active Morroniside (MOR), against alloxan (ALX)-induced genotoxicity and hyperglycaemia. prediction revealed the interaction of MOR with Poly (ADP-ribose) polymerase (PARP) protein which corroborated well with experimental L6 cell line and mice models. Data revealed the efficacy of MOR in the selective activation of PARP protein and modulating other stress proteins NF-κB, and TNF-α to initiate protective potential against ALX-induced genotoxicity and hyperglycaemia.

Physicochemical Significance of Topological Indices: Importance in Drug Discovery Research.

Background: Quantitative Structure-Activity Relationship (QSAR) studies describing the correlations between biological activity as dependent parameters and physicochemical and structural descriptors, including topological indices (TIs) as independent parameters, play an important role in drug discovery research. The emergence of graph theory in exploring the structural attributes of the chemical space has led to the evolution of various TIs, which have made their way into drug discovery. The TIs are easy to compute compared to the empirical parameters, but they lack physiochemical interpretation, which is essential in understanding the mechanism of action.

Molecular docking-based interaction studies on imidazo[1,2-a] pyridine ethers and squaramides as anti-tubercular agents.

Development of new anti-tubercular agents is required in the wake of resistance to the existing and newly approved drugs through novel-validated targets like ATP synthase, etc. The major limitation of poor correlation between docking scores and biological activity by SBDD was overcome by a novel approach of quantitatively correlating the interactions of different amino acid residues present in the target protein structure with the activity. This approach well predicted the ATP synthase inhibitory activity of imidazo[1,2-a] pyridine ethers and squaramides ( = 0.

Targeting Cysteine Proteases and their Inhibitors to Combat Trypanosomiasis.

Background: Trypanosomiasis, caused by protozoan parasites of the genus, remains a significant health burden in several regions of the world. Cysteine proteases play a crucial role in the pathogenesis of parasites and have emerged as potential therapeutic targets for the development of novel antiparasitic drugs.

Introduction: This review article aims to provide a comprehensive overview of the role of cysteine proteases in trypanosomiasis and their potential as therapeutic targets.

To Explore the Putative Molecular Targets of Diabetic Nephropathy and their Inhibition Utilizing Potential Phytocompounds.

Background: This review critically addresses the putative molecular targets of Diabetic Nephropathy (DN) and screens effective phytocompounds that can be therapeutically beneficial, and highlights their mechanistic modalities of action.

Introduction: DN has become one of the most prevalent complications of clinical hyperglycemia, with individual-specific variations in the disease spectrum that leads to fatal consequences. Diverse etiologies involving oxidative and nitrosative stress, activation of polyol pathway, inflammasome formation, Extracellular Matrix (ECM) modifications, fibrosis, and change in dynamics of podocyte functional and mesangial cell proliferation adds up to the clinical complexity of DN.

Transethosomes: Cutting edge approach for drug permeation enhancement in transdermal drug delivery system.

The skin is a major route of drug administration. Despite the high surface area of the skin, drug delivery via the skin route is problematic due to its physiological obstacles. The formulation scientist has developed a vesicular system to enhance the skin's absorption of bioactive substances.

Multi-target Polypharmacology of 4-aminoquinoline Compounds against Malaria, Tuberculosis and Cancer.

Background: Polypharmacology means drugs having interactions with multiple targets of a unique disease or many disease pathways. This concept has been greatly appreciated against complex diseases, such as oncology, CNS disorders, and anti-infectives.

Methods: The integration of diverse compounds available on public databases initiates polypharmacological drug discovery research.

Exploring the inhibitory mechanisms of indazole compounds against SAH/MTAN-mediated quorum sensing utilizing QSAR and docking.

The world is under the great threat of antimicrobial resistance (AMR) leading to premature deaths. Microorganisms can produce AMR via quorum sensing mechanisms utilizing -adenosyl homocysteine/methylthioadenosine nucleosidase (SAH/MTAN) biosynthesis. But there is no specific drug developed to date to stop SAH/MTAN, which is a crucial target for the discovery of anti-quorum sensing compound.

Stem Cell Therapy in Combination with Naturopathy: Current Progressive Management of Diabetes and Associated Complications.

Background: Diabetes is a chronic metabolic disorder having a global prevalence of nearly doubled over the last 30 years and has become one of the major health concerns worldwide. The number of adults with diabetes increased to 537 million in 2021.

Introduction: The overarching goal of diabetic research and treatment has always been to restore insulin independence and an average blood glucose level.

Repurposing of Chemotherapeutics to Combat COVID-19.

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a novel strain of SARS coronavirus. The COVID-19 disease caused by this virus was declared a pandemic by the World Health Organization (WHO). SARS-CoV-2 mainly spreads through droplets sprayed by coughs or sneezes of the infected to a healthy person within the vicinity of 6 feet.

Poly lactide-co-glycolide encapsulated nano-curcumin promoting antagonistic interactions between HSP 90 and XRCC1 proteins to prevent cypermethrin-induced toxicity: An in silico predicted in vitro and in vivo approach.

The present study describes the preparation and characterization of poly-lactide-co-glycolide encapsulated nano-curcumin (NCUR) drug, and its potential efficacy against the pesticide, such as cypermethrin-induced DNA damage and genotoxicity. Cypermethrin, the chosen pesticide, contaminates the aquatic environment after being washed off from the agricultural field to nearby water bodies leading to biomagnification-related perturbation of the ecological balance and overall environmental health by elevating adverse effects on non-target organisms producing toxic metabolites through biotransformation. The physico-chemical properties of NCUR were evaluated by employing the AFM, DLS and UV-Vis techniques.

Exploring the Targets of Novel Corona Virus and Docking-based Screening of Potential Natural Inhibitors to Combat COVID-19.

There is a need to explore natural compounds against COVID-19 due to their multitargeted actions against various targets of nCoV. They act on multiple sites rather than single targets against several diseases. Thus, there is a possibility that natural resources can be repurposed to combat COVID-19.

Current Naturopathy to Combat Alzheimer's Disease.

Neurodegeneration is the progressive loss of structure or function of neurons, which may ultimately involve cell death. The most common neurodegenerative disorder in the brain happens with Alzheimer's disease (AD), the most common cause of dementia. It ultimately leads to neuronal death, thereby impairing the normal functionality of the central or peripheral nervous system.

Molecular docking-based interactions in QSAR studies on ATP synthase inhibitors.

Tuberculosis (TB) is a global threat with a large burden across the continents in terms of mortality, morbidity, and financial losses. The disease has evolved into multi-drug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) tuberculosis owing to numerous factors ranging from patients' non-compliance to demographical implications. There have been very few new drugs for resistant TB.