Enhancement of aqueous solubility of hesperidin and naringenin utilizing hydrotropic solubilization technique: characterization and in vitro evaluation.

The therapeutic potential of two important flavonoids, i.e. hesperidin and naringenin, remains unutilized due to pharmacokinetics issues, especially poor aqueous solubility. Hydrotropic solid dispersions with different agents like sodium salicylate, niacinamide, benzoic acid, and urea etc. can change the solubility profile of poorly soluble drugs. The current study investigated the potential of different hydrotropic agents in improving the solubility of both natural bioactives. The hydrotropic solid dispersion in 1:3 w/w drug: sodium salicylate ratio showed maximum solubility and dissolution amongst all the tested hydrotropes. This novel and economical approach could be explored for other poorly soluble pharmaceuticals.

Precision medicine: Ray of hope in overcoming cancer multidrug resistance.

Multi-drug resistance (MDR) developed in response to chemotherapy is one of the prominent causes of therapeutic failure. The major underlying factors that contribute to such malignancies include tumor microenvironment, genetic alterations, changes at the cellular level and most of all the heterogeneity of tumors. Recent advances in the field of oncology have prompted a mechanistic understanding of the human genome which is responsible for such alterations, upon which the therapy would be designed. Such an approach that administers drugs by targeting the molecular changes is attributed to precision medicine. Precision medicine helps design therapy as per the requirement of patients based on the sharing of similar complex tumor environments. This revolutionized approach would help in early detection, better targeting, improved patient compliance and survival along with much reduced toxicity otherwise evidenced in conventional cancer therapy. This review discusses the cause of MDR, highlighting the role of precision medicine in overcoming such critical events. Major limitations and future prospects are also highlighted.

Recent updates on development of protein-tyrosine phosphatase 1B inhibitors for treatment of diabetes, obesity and related disorders.

The aim of this review was to discuss an overview of type 2 diabetes; biology of PTP1B; role of PTP1B in metabolic disorders; and recent updates in the development of PTP1B inhibitors reported in literature since 1994. In this study, extensive literature search was carried out on PTP1B inhibitors of natural as well as synthetic origin in various scientific databases and research articles related to discovery of PTP1B inhibitors were selected for this study. Protein tyrosine phosphatase 1B (PTP1B) is an important therapeutic target for several human diseases including type 2 diabetes, obesity and cancer because of its seminal part as a negative modulator in both insulin and leptin signaling pathways. A large number of molecules of broad chemical diversity were reported as potent and selective PTP1B inhibitors over other protein tyrosine phosphatases. Several of these molecules have shown their potential in the treatment of various human diseases including type 2 diabetes, obesity, inflammation and cancer in various animal models. But only a very limited number of PTP1B inhibitors (including ertiprotafib, trodusquemine and JTT-551) has entered clinical trials and are finally withdrawn owing to their unsatisfactory effectiveness and undesirable adverse effects. Consequently, it is still highly imperative and of great importance to develop potent, highly selective and safe PTP1B inhibitors.

Identification of novel signal of Raynaud's phenomenon with Calcitonin Gene-Related Peptide(CGRP) antagonists using data mining algorithms and network pharmacological approaches.

BACKGROUND: Calcitonin gene-related peptide (CGRP) antagonists are recently approved for the treatment of migraine. AIM: The main aim of the current study was to find out the association of CGRP antagonists with RP using data mining algorithms integrated with network pharmacological approaches. RESEARCH DESIGN AND METHODS: The individual case safety reports were extracted using OpenVigil2.1-MedDRA-V17 (2004Q1-2022Q3), the United States Adverse Event Reporting System (US FAERS). The data mining algorithms i.e. reporting odds ratio (ROR) with 95% confidence and proportionality reporting ratio (PRR) with associated chi-square value were calculated along with a minimum of three ICSRs to identify the signal. Further, the network was constructed using Cytoscape 3.7.2. Finally, molecular docking was performed using Glide, Schrodinger Inc. RESULTS: The PRR ≥2 with a linked chi-square value ≥4, add up of co-occurrence ≥3, and a lower limit of 95% confidence interval of ROR exceeding 2 indicates a positive signal of RP. Further, the network pharmacological and molecular docking results have shown the involvement of insulin-like growth factor 1-receptor (IGF1R) pathways. CONCLUSION: The RP is recognized as a novel signal with all CGRP antagonists.

Synthetic and Natural Radioprotective Agents: Recent Status and their Underlying Mechanism of Action.

Various substances possessing radiation scavenging properties, known as radioprotectors, play a crucial role in shielding organisms from the harmful effects of ionizing radiation (IR) by preventing cellular damage caused by free radicals. Initially, synthetic radioprotectors were developed using thiol synthetic compounds. However, among these, only amifostine (WR-2721) underwent clinical testing as a radioprotector. Various composites with different chemical structures other than thiol compounds were also investigated. However, synthetic radioprotectors are known to be associated with severe side effects, which lead to an inclination towards natural substances. Plants and natural products have emerged as promising sources of radioprotectors, renowned for their non-toxic nature across a broad range of doses and their cost-effectiveness. Radioprotectors are employed in diverse pharmaceutical approaches to mitigate the toxicities induced by radiation. The present review encompasses a detailed account of various synthetic and naturally occurring compounds possessing radioprotective properties, and different investigations related to their radioprotective action, ranging from free radicals scavenging to gene therapy, have also been precisely covered. Numerous radioprotectors have different mechanisms of action, and have proven benefits of naturally occurring compounds over chemically synthesized ones.

Unlocking the potential of oncology biomarkers: advancements in clinical theranostics.

INTRODUCTION: Cancer biomarkers have revolutionized the field of oncology by providing valuable insights into tumor changes and aiding in screening, diagnosis, prognosis, treatment prediction, and risk assessment. The emergence of "omic" technologies has enabled biomarkers to become reliable and accurate predictors of outcomes during cancer treatment. CONTENT: In this review, we highlight the clinical utility of biomarkers in cancer identification and motivate researchers to establish a personalized/precision approach in oncology. By extending a multidisciplinary technology-based approach, biomarkers offer an alternative to traditional techniques, fulfilling the goal of cancer therapeutics to find a needle in a haystack. SUMMARY AND OUTLOOK: We target different forms of cancer to establish a dynamic role of biomarkers in understanding the spectrum of malignancies and their biochemical and molecular characterization, emphasizing their prospective contribution to cancer screening. Biomarkers offer a promising avenue for the early detection of human cancers and the exploration of novel technologies to predict disease severity, facilitating maximum survival and minimum mortality rates. This review provides a comprehensive overview of the potential of biomarkers in oncology and highlights their prospects in advancing cancer diagnosis and treatment.

Therapeutic Potential of Catechin as an IKK-ß Inhibitor for the Management of Arthritis: In vitro and In vivo Approach.

Background: Rheumatoid arthritis (RA) is associated with increased levels of cytokines, for instance, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and interleukin-1 (IL-1), which exhibit potent pro-inflammatory effects and are contributing factors to disease progression. A range of cytokines, cell adhesion molecules, and enzymes that are implicated in the debilitating effects of RA are transcribed by nuclear factor kappa. Objectives: The purpose of this research was to characterize the efficacy of "catechin" as an IkappaB kinase-beta (IKK-ß) inhibitor in collagen-induced arthritis (CIA) model in mice, as IKK-ß is crucial in the transmission of signal-inducible NF-κß activation. Methods: Arthritis was brought on in Bagg and Albino, but it is written BALB/c (BALB/c) male mice through subcutaneous immunization with bovine type II collagen on days 0 and 21. Catechin is given orally every day after the onset of the disease. Clinical evaluation of the prevalence and severity of the condition was done throughout the trial, and biochemical testing was done at the end (day 42). Results: In vitro findings of the study demonstrated catechin as a potent inhibitor of IKK-ß with Half maximal Inhibitory Concentration (IC50) values of 2.90 µM and 4.358 µM in IKK-ß and NF-κß transactivation activity assay, respectively. Furthermore, catechin (dose range of 10-100 mg/kg, p.o.) was effective in reducing disease incidence and clinical signs in a dose-dependent manner, with an Effective Dose for 50% of the population (ED50) value of 79.579 mg/kg. The findings of this study demonstrate dose-dependent efficacy in terms of both disease severity (clinical scoring) and inflammatory markers (biochemical evaluation of the serum and joints). Conclusions: IKK inhibitors are a prospective target for the creation of new therapeutics for arthritis and other inflammatory diseases because it has been suggested that this enzyme is crucial in the pathophysiology of RA. The finding of this study suggests that "catechin" represents a novel inhibitor of IKK-ß with promising anti-inflammatory activity.

Structure-based virtual screening for identification of potential CDC20 inhibitors and their therapeutic evaluation in breast cancer.

Cell division cycle 20 (CDC20), a critical partner of anaphase promoting complex (APC/C), is indispensably required for metaphase-to-anaphase transition. CDC20 overexpression in TNBC breast cancer patients has been found to be correlated with poor prognosis, hence, we aimed to target CDC20 for TNBC therapeutics. In silico molecular docking of large-scale chemical libraries (phytochemicals/synthetic drugs) against CDC20 protein structure identified five synthetic drugs and four phytochemicals as potential hits interacting with CDC20 active site. The molecular selection was done based on docking scores, binding interactions, binding energies and MM/GBSA scores. Further, we analysed ADME profiles for all the hits and identified lidocaine, an aminoamide anaesthetic group of synthetic drug, with high drug-likeness properties. We explored the anti-tumorigenic effects of lidocaine on MDA-MB-231 TNBC breast cancer cells, which resulted in increased growth inhibition in dose-dependent manner. The molecular mechanism behind the cell viability defect mediated by lidocaine was found to be induction of G2/M cell cycle arrest and cellular apoptosis. Notably, lidocaine treatment of TNBC cells also resulted in downregulation of CDC20 gene expression. Thus, this study identifies lidocaine as a potential anti-neoplastic agent for TNBC cells emphasizing CDC20 as a suitable therapeutic target for breast cancer. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03554-7.

Association of temozolomide with progressive multifocal leukoencephalopathy: a disproportionality analysis integrated with network pharmacology.

BACKGROUND: Temozolomide (TMZ) is an alkylating agent approved for the management of glioblastoma. The TMZ is not known for progressive multifocal leukoencephalopathy (PML). The main objective of the current study is to find out the association of TMZ with PML using disproportionality analysis of FDA Adverse Event Reporting System (FAERS) data integrated with network pharmacological approaches. RESEARCH DESIGN AND METHODS: OpenVigil tool was used to query the FAERS database. The disproportionality measures were calculated. The network has been constructed using Cytoscape. Finally, the possible binding interactions were studied using Glide, Schrödinger Inc. RESULTS: A total number of 3502 cases of PML were reported in the FAERS database. Out of these, 10 cases were found with TMZ. The subgroup analysis results have shown a greater number of cases in females. The network has indicated the involvement of human mitogen-activated protein kinase, 3-phosphoinositide-dependent protein kinase 1 protein, human mTOR complex protein, phosphatidylinositol 4,5-bisphosphate 3-kinase protein, and glycogen synthase kinase-3 beta protein. The docking results have indicated good interactions of TMZ with active site of glycogen synthase kinase-3 beta and mitogen-activated protein kinase 1 as compared to other identified targets. CONCLUSION: The PML is identified as novel signal with temozolomide.

Virtual screening and antimicrobial evaluation for identification of natural compounds as the prospective inhibitors of antibacterial drug resistance targets in Staphylococcus aureus.

Infectious diseases have remained a burgeoning cause of death and disability since long. Staphylococcus aureus (S. aureus) is a severe bacterial pathogen causing nosocomial and community infections. It exhibits widespread resistance to antibiotics posing a significant threat to their efficacy. For combating this challenge, different strategies may include modifying existing antibiotics, developing new antibacterial agents, and combining treatments with resistance mechanism inhibitors. Resistance in S. aureus occurs through horizontal gene transfer or chromosomal mutations. Acquisition mechanisms involve enzymatic modification, efflux, target bypass, and drug displacement. Mutations can impact drug targets, activate efflux pumps, or alter cell wall composition to impede drug access. Overcoming S. aureus resistance requires innovative approaches to preserve antibiotic effectiveness. The present study involves the virtual screening of phytochemicals of diverse chemical classes from Zinc database against the antibiotic resistant targets of S. aureus like ß-Lactamase, Penicillin Binding Protein 2a (PBP2a), Dihydrofolate reductase (DHFR), DNA gyrase, Multidrug ABC transporter SAV1866, Undecaprenyl diphosphate synthase (UPPS), etc. Thymol, eugenol, gallic acid, l-ascorbic acid, curcumin, berberine and quercetin were identified as potential molecules based on their docking score, binding interactions. These molecules were further analyzed for the ADMET and drug likeness properties using pkCSM, SwissADME and Qikprop tools. Further in vitro evaluation of these molecules against antibiotic-resistant strains of S. aureus, both alone and in combination with antibiotics revealed significant findings. Curcumin demonstrated the lowest MIC values (31.25-62.5 µg/ml) when tested individually. Thymol, berberine, and quercetin displayed MIC values within the range of 125-250 µg/ml, while eugenol and gallic acid exhibited MIC values ranging from 500 to 1000 µg/ml. Notably, thymol exhibited potent synergy with all four antibiotics against clinical isolates of S. aureus, with Fractional inhibitory concentration index (FICI) values consistently below 0.5, highlighting its exceptional antibacterial activity, especially in combination with amoxicillin.

Structure-based virtual screening of chemical libraries as potential MELK inhibitors and their therapeutic evaluation against breast cancer.

New targeted therapy for triple negative breast cancer (TNBC) is an urgent need, as advanced disease responds poorly to conventional chemotherapy. Genomic and proteomic studies are currently investigating new genes and proteins as promising therapeutic targets. One of such therapeutic targets is a cell cycle regulatory kinase; Maternal Embryonic Leucine Zipper Kinase (MELK), overexpressed in TNBC and correlated with cancer development. We performed molecular docking for virtual screening of chemical libraries (phytochemicals/synthetic drugs) against MELK protein structure and identified 8 phytoconstituents (isoxanthorin, emodin, gamma-coniceine, quercetin, tenuazonic acid, isoliquiritigenin, kaempferol, and Nobiletin) and 8 synthetic drugs (tetrahydrofolic acid, alfuzosin, lansoprazole, ketorolac, ketoprofen, variolin B, orantinib, and firestein) as potential hits interacting with the active site residues of MELK based on bound poses, hydrogen bond, hydrophobic interactions and MM/GBSA binding free energies. ADME and drug-likeness prediction further identified few hits with high drug-likeness properties and were further tested for anti-tumorigenic potential. Two phytochemicals isoliquiritigenin and emodin demonstrated growth inhibitory effects on TNBC MDA-MB-231 cells while much lower effect was observed on non-tumorigenic MCF-10A mammary epithelial cells. Treatment with both molecules downregulated MELK expression, induced cell cycle arrest, accumulated DNA damage and enhanced apoptosis. The study identified isoliquiritigenin and emodin as potential MELK inhibitors and provides a basis for subsequent experimental validation and drug development against cancer.

Exploring Phytochemicals from Himalayan Medicinal Plants as Novel Therapeutic Agents.

Over-prescription of medicines leads to some crucial health issues like resistance, non-specificity, etc. Therefore, a human consumes various natural foods, therapeutics, and nutritional supplements to combat this problem. Various therapeutic properties of secondary metabolites, such as anticancer, anti-inflammatory, and antibacterial properties, are important in drug discovery and medicinal application. These natural products have replaced synthetic materials, resulting in a great deal of sustainability, rational use, and preservation of biodiversity. This review described the potential therapeutic applications of secondary plant metabolites found in Himalayan Indian plants. The database contains 45 plants to treat various diseases, such as cancer, inflammation, and microbial infections. Besides authorized ITIS names, it includes Hindi names, family names, and active constituents. The most important information about the molecules can be found in the hyperlinks for the active constituents. It includes structures (two-dimensional and threedimensional), names and identifiers, chemical and physical properties, spectral information, biochemistry, literature and patents. The review also references various phytochemicals responsible for preventing COVID-19. Despite several challenges in manufacturing natural products, researchers may conduct research to produce successful medicines with few side effects.

Natural alkaloids targeting EGFR in non-small cell lung cancer: Molecular docking and ADMET predictions.

The phytochemicals contribute to the processes of protection and interaction by acting as antioxidants, anti-mutagens, anticarcinogens, and antimicrobial agents. Among the diverse families of phytoconstituents, alkaloids play an essential role in medicine. These are low-molecular-mass compounds containing nitrogen and are generally alkaline. In this study, in silico molecular docking was performed using AutoDock Vina for thirty-one alkaloids against epidermal growth factor receptor (EGFR). Erlotinib was used as a reference ligand for this study. Erlotinib has been linked to various serious side effects over the past decade, including folliculitis, diarrhoea, paronychia, fatigue, conjunctivitis, ectopion, and epiphora of the lower eyelids. This study found sanguinarine (-10.7 kcal mol-1) to be the most potent inhibitor of EGFR as compared to erlotinib (-7.5 kcal mol-1). Other alkaloids namely, isocolumbin (-9.3 kcal mol-1), lunamarine (-9.1 kcal mol-1), ajmaline (-8.6 kcal mol-1), magnoflorine (-8.6 kcal mol-1) and jatrorrhizine (-8.5 kcal mol-1) also showed potent inhibition against EGFR, but the stability of these molecules with EGFR was less than sanguinarine and more than erlotinib. These were stable and ideal pharmaceutical alkaloids because of their significant interactions, minimal Gibbs free energy, safety, effectiveness and selectivity. Amongst the 31 alkaloids subjected to ADMET prediction, 29 alkaloids followed Lipinski's rule of five. These 29 alkaloids were predicted to have high bioavailability, high lead-likeness score, low toxicity and were easier to synthesize. Compared to erlotinib, other molecules showed less or no inhibition of EGFR. The six named compounds listed above may be potent inhibitors for EGFR mutated cancers, as for example non-small cell lung cancer, colorectal cancer, and pancreatic cancer.

Repurposing Drugs as Novel Triple-negative Breast Cancer Therapeutics.

BACKGROUND: Triple-Negative Breast Cancer (TNBC) is the most aggressive form of Breast Cancer (BC), with high rates of metastasis and recurrence and limited treatment options. Chemotherapy and radiotherapy, for example, have several harmful side effects, and no FDA-approved therapies are currently available. Repurposing old clinically approved drugs to target various TNBC targets is a novel method that has fewer side effects and leads to successful, low-cost drug development in a shorter amount of time. Medicinal plants containing various phytoconstituents (flavonoids, alkaloids, phenols, essential oils, tannins, glycosides, lactones) play a very crucial role in combating various types of diseases and are used in the drug development process because of having lesser side effects. OBJECTIVE: The present review summarizes various categories of repurposed drugs that target multiple targets of TNBC, as well as phytochemical categories that target TNBC singly or in combination with old synthetic drugs. METHODS: Literature information was collected from various databases such as Pubmed, Web of Science, Scopus, and Medline to understand and clarify the role and mechanism of repurposed synthetic drugs and phytoconstituents against TNBC by using keywords like "breast cancer", "repurposed drugs", "TNBC" and "phytoconstituents". RESULTS: Various repurposed drugs and phytochemicals that target different signaling pathways and exert their cytotoxic activities on TNBC cells ultimately lead to cell apoptosis, reducing the recurrence rate and stopping the metastasis process. CONCLUSION: Inhibitory effects can be seen at various levels, providing information and evidence to researchers in the drug development process. As a result, more research and investigations are needed to develop better therapeutic treatment options for TNBC.

Recent Advances in Nanomaterials of Group XIV Elements of Periodic Table in Breast Cancer Treatment.

Breast cancer is one of the most common malignancies and a leading cause of cancer-related mortality among women worldwide. The elements of group XIV in the periodic table exhibit a wide range of chemical manners. Recently, there have been remarkable developments in the field of nanobiomedical research, especially in the application of engineered nanomaterials in biomedical applications. In this review, we concentrate on the recent investigations on the antiproliferative effects of nanomaterials of the elements of group XIV in the periodic table on breast cancer cells. In this review, the data available on nanomaterials of group XIV for breast cancer treatment has been documented, providing a useful insight into tumor biology and nano-bio interactions to develop more effective nanotherapeutics for cancer patients.

Development of lipid-based nanoparticles for enhancing the oral bioavailability of paclitaxel.

The current research work investigates the potential of solid lipid nanoparticles (SLNs) in improving the oral bioavailability of paclitaxel. Paclitaxel-loaded SLNs (PTX-SLNs) were prepared by modified solvent injection method using stearylamine as lipid, soya lecithin and poloxamer 188 as emulsifiers. SLNs were characterized in terms of surface morphology, size and size distribution, surface chemistry and encapsulation efficiency. Pharmacokinetics and bioavailability studies were conducted in male Swiss albino mice after oral administration of PTX-SLNs. SLNs exhibited spherical shape with smooth surface as analyzed by transmission electron microscopy (TEM). The mean particle size of SLNs was 96 ± 4.4 nm with a low polydispersity index of 0.162 ± 0.04 and zeta potential of 39.1 ± 0.8 mV. The drug entrapment efficiency was found to be 75.42 ± 1.5% with a loading capacity of 31.5 ± 2.1% (w/w). Paclitaxel showed a slow and sustained in vitro release profile and followed Higuchi kinetic equations. After oral administration of the PTX-SLNs, drug exposure in plasma and tissues was ten- and twofold higher, respectively, when compared with free paclitaxel solution. PTX-SLNs produced a high mean C (max) (10,274 ng/ml) compared with that of free paclitaxel solution (3,087 ng/ml). The absorbed drug was found to be distributed in liver, lungs, kidneys, spleen, and brain. The results suggested that PTX-SLNs dispersed in an aqueous environment are promising novel formulations that enhanced the oral bioavailability of hydrophobic drugs, like paclitaxel and were quite safe for oral delivery of paclitaxel as observed by in vivo toxicity studies.

Protective Effect of Dalbergia sissoo Extract Against Amyloid-ß (1-42)-induced Memory Impairment, Oxidative Stress, and Neuroinflammation in Rats.

OBJECTIVES: The ayurvedic literature reports that Dalbergia sissoo, a common medicinal plant for gastric and skin problems, has brain-revitalizing effects. However, the neuroprotective effect of this herb on an amyloid-ß (Aß) 1-42 model of Alzheimer's disease (AD) is yet unknown. The current study describes the protective effect of ethanolic extracts of D. sissoo leaves (EEDS) against Aß (1-42)-induced cognitive deficit, oxidative stress, and neuroinflammation in rats. MATERIALS AND METHODS: EEDS (300 and 500 mg/kg) was orally administered to rats for 2 weeks prior to intracerebroventricular Aß (1-42) treatment. The neuroprotective effect of EEDS was assessed by evaluating behavioral, biochemical, and neuroinflammatory parameters in the rat hippocampus. Memory function was assessed via the Morris water maze (MWM) task 2 weeks after Aß (1-42) administration. After 3 weeks, surgery was performed, all biochemical parameters were evaluated, and histopathological examination of the tissues was carried out. RESULTS: EEDS improved the cognitive ability of Aß (1-42)-administered rats in the MWM task. It reduced oxidative stress by significantly decreasing nitrite and malondialdehyde levels and increasing catalase activity and glutathione levels in the rat brain. Moreover, EEDS mitigated neuroinflammation in rats by decreasing the concentration of neuroinflammatory markers in a dose-dependent manner. CONCLUSION: D. sissoo leaf extract has a beneficial role in alleviating cognitive deficits in AD by modulating cholinergic function, oxidative stress, and neuroinflammation.

Albumin-Coated Mesoporous Silica Nanoparticles of Docetaxel: Preparation, Characterization, and Pharmacokinetic Evaluation.

The potential of albumin-coated hollow mesoporous silica nanoparticles (A-HMSNs) to optimize the chemotherapeutic efficacy of docetaxel (DTX) was explored. The synthesized A-DTX-HMSNs had a nanometric size range, offered large surface area with numerous pores, and offered high drug entrapment and loading, that is, 79.18% ± 1.4% and 19.11% ± 1.30%, respectively. Fourier transform infrared spectroscopy and differential scanning calorimetry studies confirmed drug loading and the presence of albumin onto the developed systems, and the drug release followed Higuchi profile. A-HMSNs significantly enhanced the pharmacokinetic profile of DTX by eightfold vis-à-vis the pure DTX. The enhanced plasma levels (Cmax, Tmax, area under the curve), prolonged drug release, long circulation time, lower clearance, hemocompatability, and substantially higher drug loading offered by these nanocarriers inherit promise of a safer and efficacious formulation of DTX.

Role of phytoconstituents in the management of COVID-19.

BACKGROUND: COVID-19, a severe global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged as one of the most threatening transmissible disease. As a great threat to global public health, the development of treatment options has become vital, and a rush to find a cure has mobilized researchers globally from all areas. SCOPE AND APPROACH: This review focuses on deciphering the potential of different secondary metabolites from medicinal plants as therapeutic options either as inhibitors of therapeutic targets of SARS-CoV-2 or as blockers of viral particles entry through host cell receptors. The use of medicinal plants containing specific phytomoieties could be seen in providing a safer and long-term solution for the population with lesser side effects. Key Findings and Conclusions: Considering the high cost and time-consuming drug discovery process, therapeutic repositioning of existing drugs was explored as treatment option in COVID-19, however several molecules have been retracted as therapeutics either due to no positive outcomes or the severe side effects. These effects call for exploring the alternate treatment options which are therapeutically effective as well as safe. Keeping this in mind, phytopharmaceuticals derived from medicinal plants could be explored as important resources in the development of COVID-19 treatment, as their role in the past for treatment of viral diseases like HIV, MERS-CoV, and influenza has been well reported. Considering this fact, different phytoconstituents such as flavonoids, alkaloids, tannins and glycosides etc. Possessing antiviral properties against coronaviruses and possessing potential against SARS-CoV-2 have been reviewed in the present work.

Novel Cinnamic Acid Derivatives as Potential PPARδ Agonists for Metabolic Syndrome: Design, Synthesis, Evaluation and Docking Studies.

BACKGROUND: Peroxisome proliferator-activated receptor (PPAR) δ is expressed universally in the entire tissues, particularly in those concerned with the lipid metabolism. PPAR δ stimulation alters body's energy fuel preference to fat from glucose and shows up as an emerging pharmacological target for the treatment of metabolic disorders. METHODS: A new series of cinnamic acid derivatives was synthesized and evaluated for the antidiabetic and antiinflammatory activities in the animal models followed by in silico docking studies to determine the binding interactions for the best fit conformations in the binding site of the PPARδ protein. RESULTS: Amongst the synthesized molecules, compound 3 showed higher antidiabetic activity in oral glucose tolerance test and compound 1 showed higher antiinflammatory activity in the carrageenan induced rat paw oedema method. The in vivo study results were supported by the similar in silico molecular docking results. Most of the synthesized derivatives showed drug likeness as depicted via Lipinski's rule of 5. CONCLUSION: These molecules can serve as the early hit molecules for the discovery of safe, effective and bioavailable PPARδ agonists for the potential treatment of various metabolic disorders.