Examining the Pre- and Post-percutaneous Coronary Intervention Blood Pressure Variability Using Ambulatory Blood Pressure Monitoring in Patients With Stable and Unstable Coronary Artery Disease.

Introduction The World Health Organization has drawn attention to the fact that coronary artery disease (CAD) is our modern "epidemic." Nowadays, sudden death during sleep has become prevalent due to a lack of oxygen supply to the heart. CAD causes more deaths and disabilities and incurs greater economic costs than any other illness in the developed world. The prevalence of cardiovascular disorders and heart disease is on the rise in India. Hypertension is one of the leading risk factors for all cardiovascular diseases. This study aims to compare blood pressure variability before and after percutaneous coronary intervention (PCI), using ambulatory blood pressure monitoring (ABPM) in patients with stable and unstable CAD. Materials and methods This prospective observational study was conducted among 52 patients with stable and unstable CAD, admitted to the medicine department, who required PCI at a tertiary care hospital. Before and after PCI, the same antihypertensive drugs were orally administered. ABPM was performed before PCI and one day after PCI. ABPM was conducted every 30 minutes during the day and every 60 minutes during the night over a 24-hour period using a mobil-o-graph (IEM, Germany). The results of the observed parameters were analyzed using the HMS Client-Server 4.0 system (Informer Technologies, Inc., Los Angeles, USA). The collected data were analyzed using SPSS Statistics version 21.0 software (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.). Results Out of 52 patients, 28 (53.8%) had stable CAD and 24 (46.2%) had unstable CAD. The mean age of patients with stable and unstable CAD was 56.64±9.44 and 57.04±12.36 years, respectively. The majority of patients with stable (67.9%) and unstable CAD (62.5%) were males. Various other variables were considered, such as lipid profile, blood sugar, cardiac troponin-I, and medical history, including hypertension and type 2 diabetes mellitus. Among stable CAD patients, a comparison between pre- and post-PCI systolic blood pressure (SBP) did not show a significant difference in all SBP measurements (p>0.05). However, the mean diurnal index was significantly lower following PCI compared to before PCI (p=0.019). Among unstable CAD patients, a comparison between pre- and post-PCI SBP showed a significant change in peak daytime, average daytime, and diurnal index (p<0.05). For all other SBP measurements, the difference between pre- and post-PCI measurements was not statistically significant (p>0.05). In patients with stable CAD, a statistically significant change in diastolic blood pressure (DBP) following PCI was observed for peak daytime, peak nighttime, and average nighttime values. In contrast, for patients with unstable CAD, a statistically significant change in DBP following PCI was observed for peak daytime, peak nighttime, and minimum daytime values (p<0.05). Statistically, post-PCI, there was no significant difference between the two groups for SBP and DBP measurements (p>0.05). Additionally, there was no significant difference between the two groups pre- and post-PCI in the pattern of dipping. Conclusion A comparison of the ABPM before and after PCI showed that, within 48 hours post-PCI, the ambulatory blood pressure indicators did not differ statistically from those before PCI.

Pyrazoles as Anti-inflammatory and Analgesic Agents: In-vivo and In-silico Studies.

BACKGROUND: Pyrazole is a well-known nucleus in the pharmacy field with a wide range of other activities in addition to anti-inflammatory and analgesic, i.e., anticonvulsant, antiviral, and anticancer activities. There are well-known marketed drugs having pyrazole moiety as celecoxib, and lonazolac as COX-II inhibitors. AIMS: We aim to synthesize better anti-inflammatory than existing ones. Thiophene is also known for its analgesic and anti-inflammatory action. Thus, the fusion of both gives better anti-inflammatory agents. In the present studies, derivatives from two series of pyrazole were prepared by reacting substituted chalcone (3a-3f) derivatives prepared from 2-acetyl thiophene. They substituted aromatic aldehydes with phenyl hydrazine to form (5a-5f) and with 2, 4-dinitro phenyl hydrazine giving compounds (6a-6f) separately. METHODS: Purified and characterized pyrazoles have been analyzed for in-vivo analgesic and anti-inflammatory activities by using standard methods. Compounds 5e, 5f, and 6d were proved to be potent analgesics and series (5a-5f) was found to have anti-inflammatory action, which was further validated using docking and ADME studies. RESULTS: The ADME profile of synthesized compounds was found to be satisfactory. CONCLUSION: The synthesized compounds can serve as lead for further drug designing.

Selenium levels in colorectal cancer: A systematic review and meta-analysis of serum, plasma, and colorectal specimens.

BACKGROUND: Colorectal cancer (CRC) is a growing public health problem. Several clinical studies have shown a potentially protective effect of selenium (Se), but the reports are inconsistent. The objective of the study was to examine the evidence for relation between serum/tissue Se status and CRC. METHOD AND MATERIALS: In this Systematic Review and Meta-Analysis, we searched Cochrane Library, EBSCOhost, EMBASE, ProQuest, PubMed/MEDLINE, Scopus, and Web of Science for studies reporting serum/plasma/whole blood/tissue Se concentrations in CRC patients and controls for articles published till August 2023. Meta-analysis was performed, and study quality, heterogeneity, and small study effects were assessed. Based on a random effects model, summary mean differences in serum levels of Se between CRC patients and healthy controls, and Se levels between malignant and matched non-malignant tissue specimens were assessed. RESULTS: After initial screening, a total of 24 studies (18 serum and 6 tissue studies) with a pooled total of 2640 participants were included in the meta-analysis. CRC patients had significantly lower serum Se levels than healthy controls, being the difference between the two equal to 3.73 µg/dl (95% CI: 6.85-0.61). However, the heterogeneity was very high, I2= 99% (p < 0.01). Our meta-analysis showed higher Se levels in CRC cancerous specimens than in matched healthy colon tissue: the increase was equal to 0.07 µg/g wet tissue weight (95% CI: 0.06-0.09; p= 0.02). CONCLUSIONS: CRC patients have lower serum and higher colon cancerous tissue Se levels. Some factors, such as Se levels in different tumor grades of CRC need to be further considered for a more conclusive association between Se levels and risk of CRC.

Unlocking the Pharmacological Potential of Benzimidazole Derivatives: A Pathway to Drug Development.

Heterocyclic molecules have fascinated a massive interest in medicinal chemistry. They are heterocyclic compounds that have gained significance due to their diverse variety of pharmacological activities. Benzimidazole is a heterocyclic compound consisting of benzene and imidazole rings. The ease of synthesis and the structural versatility of benzimidazole make it a promising scaffold for drug development. Many biological actions of benzimidazole derivatives have been well documented, including antibacterial, antiviral, anticancer, anti-inflammatory, antitubercular, and anthelmintic properties. The mechanism of action of benzimidazole derivatives varies with their chemical structure and target enzyme. This review has explored numerous methods for producing benzimidazole derivatives as well as a broad range of pharmacological activities. SAR investigations are also discussed in this review as they provide crucial details regarding the essential structural qualities that benzimidazole derivatives must have in order to be biologically active, which could aid in the rational design of new drug candidates. Benzimidazole scaffold is an exclusive structure in drug design and discovery. Many new pharmaceutical drugs containing benzimidazole are anticipated to be available within the next ten years as a result of the extensive therapeutic applications of benzimidazole and its derivatives. This review inspired many researchers to develop more biologically active compounds bearing benzimidazole, expanding the scope of finding a remedy for other diseases. From this study, we concluded that 2-substituted benzimidazole was considered more extensively by researchers.

Potential use of cidofovir, brincidofovir, and tecovirimat drugs in fighting monkeypox infection: recent trends and advancements.

Recent years have witnessed the rise of more recent pandemic outbreaks including COVID-19 and monkeypox. A multinational monkeypox outbreak creates a complex situation that necessitates countermeasures to the existing quo. The first incidence of monkeypox was documented in the 1970s, and further outbreaks led to a public health emergency of international concern. Yet as of right now, neither vaccines nor medicines are certain to treat monkeypox. Even the inability of conducting human clinical trials has prevented thousands of patients from receiving effective disease management. The current state of the disease's understanding, the treatment options available, financial resources, and lastly international policies to control an epidemic state are the major obstacles to controlling epidemics. The current review focuses on the epidemiology of monkeypox, scientific ideas, and available treatments, including potential monkeypox therapeutic methods. As a result, a thorough understanding of monkeypox literature will facilitate in the development of new therapeutic medications for the prevention and treatment of monkeypox.

Serum copper status of patients with colorectal cancer: A systematic review and meta-analysis.

BACKGROUND: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and a public health problem. Several clinical studies have shown that copper (Cu) is involved in carcinogenesis, possibly via cuproptosis, a new form of programmed cell death, but the conclusions from published reports are inconsistent. This study aimed at evaluating the potential of Cu dysregulation as a CRC susceptibility factor. METHODS: In this systematic review and meta-analysis, we searched Cochrane Library, EBSCOhost, EMBASE, ProQuest, PubMed/MEDLINE, Scopus, and Web of Science for studies reporting serum Cu concentrations in CRC patients and controls from articles published till June 2023. The studies included reported measurements of serum/plasma/blood Cu levels. Meta-analyses were performed as well as study quality, heterogeneity, and small study effects were assessed. Based on a random effects model, summary standardized mean differences (SMDs) and the corresponding 95% confidence intervals (95% CIs) were applied to compare the levels of Cu between CRC patients and controls. RESULTS: 26 studies with a pooled total of9628 participants and 2578 CRC cases were included. The pooled SMD was equal to 0.85 (95% CIs -0.44; 2.14) showing that the CRC patients had higher mean Cu levels than the control subjects, but the difference was not significant (p = 0.185) and the heterogeneity was very high, I2 = 97.9% (95% CIs: 97.5-98.3%; p < 0.001). CONCLUSION: The pooled results were inconclusive, likely due to discordant results and inaccuracy in reporting data of some studies; further research is needed to establish whether Cu dysregulation might contribute to the CRC risk and whether it might reflect different CRC grades.

Melittin: a possible regulator of cancer proliferation in preclinical cell culture and animal models.

BACKGROUND: Melittin is a water-soluble cationic peptide derived from bee venom that has been thoroughly studied for the cure of different cancers. However, the unwanted interactions of melittin produce hemolytic and cytotoxic effects that hinder their therapeutic applications. To overcome the shortcomings, numerous research groups have adopted different approaches, including conjugation with tumor-targeting proteins, gene therapy, and encapsulation in nanoparticles, to reduce the non-specific cytotoxic effects and potentiate their anti-cancerous activity. PURPOSE: This article aims to provide mechanistic insights into the chemopreventive activity of melittin and its nanoversion in combination with standard anti-cancer drugs for the treatment of cancer. METHODS: We looked over the pertinent research on melittin's chemopreventive properties in online databases such as PubMed and Scopus. CONCLUSION: In the present article, the anti-cancerous effects of melittin on different cancers have been discussed very nicely, as have their possible mechanisms of action to act against different tumors. Besides, it interacts with different signal molecules that regulate the diverse pathways of cancerous cells, such as cell cycle arrest, apoptosis, metastasis, angiogenesis, and inflammation. We also discussed the recent progress in the synergistic combination of melittin with standard anti-cancer drugs and a nano-formulated version of melittin for targeted delivery to improve its anticancer potential.

Might Diet, APOE-APOA1 Axis, and Iron Metabolism Provide Clues About the Discrepancy in Alzheimer's Disease Occurrence Between Humans and Chimpanzees? A Bioinformatics-Based Re-Analysis of Gene Expression Data on Mice Fed with Human and Chimpanzee Diets.

The emergence of conflicting reports on the natural occurrence of Alzheimer's disease (AD) in non-human primates has prompted research on the comparison of the role of diet-associated changes in gene expression between humans and non-human primates. This article analyzes the effects of different human and chimpanzee diets and their link with apolipoproteins, lipid, and iron (Fe) metabolism, starting from available data, to find out any gap in the existing knowledge. By using a system biology approach, we have re-analyzed the liver and brain RNA seq data of mice fed with either human or chimpanzee diet for 2 weeks to look for genetic differences that may explain the differences in AD occurrence between those two classes. In liver samples of mice fed with the chimpanzee diet in comparison to the human diet, apolipoprotein A-1, ceruloplasmin, and 10 other genes were upregulated while 21 genes were downregulated. However, brain apolipoprotein E4 gene expression was not changed upon diet. Genetic, structural, and functional differences in apolipoprotein E protein, along with differences in Fe metabolisms and a longer lifespan of humans during evolution may account for the observed disparity.

Prevalence of mpox viral DNA in cutaneous specimens of monkeypox-infected patients: a systematic review and meta-analysis.

Background: Human monkeypox (mpox) disease is a multicountry outbreak driven by human-human transmission which has resulted in an international public health emergency. However, there is limited evidence on the positivity rate of skin lesions for mpox viral DNA. We aim to fill this gap by estimating the pooled positivity rate of skin samples with mpox viral DNA from mpox patients globally. Methods: In this systematic review and meta-analysis, seven databases and several preprint servers have been extensively searched until 17 January 2023 according to a prospectively registered protocol (PROSPERO: CRD42023392505). Articles including the positivity rate of skin samples with mpox viral DNA in mpox-confirmed patients were considered eligible. After a quality assessment, a random-effect meta-analysis was used for pooled prevalence. To explore and resolve heterogeneity, we used statistical methods for outlier detection, influence analysis, and sensitivity analysis. Findings: Among the 331 articles retrieved after deduplication, 14 studies were finally included. The pooled positivity rate of the skin samples was 98.77% (95% CI: 94.74%-99.72%). After the removal of an influential outlier, I 2 for heterogeneity dropped from 92.5% to 10.8%. Meta-regression did not reveal any significant moderator. Conclusion/interpretation: The present findings reinforce that skin lesions act as a reservoir of mpox viral DNA and contribute to a high infectivity risk. This may be a prevailing basis of prompt transmission during the current multicountry outbreak and also needs further investigation. The present imperative outcome may benefit in producing valuable preventive and management procedures in an appropriate health strategy.

Wogonin, as a potent anticancer compound: From chemistry to cellular interactions.

Chinese native medicine Scutellaria baicalensis Georgi, also referred to as Chinese skullcap or Huang-Qin, is frequently used to treat cancer, viral infections, and seizures. This plant's abundance of flavones (wogonoside) and their related aglycones (wogonin) is responsible for many of its pharmacologic effects. A significant ingredient in S. baicalensis that has been the subject of the most research is wogonin. Numerous preclinical investigations revealed that wogonin suppresses tumor growth by cell cycle arrest, stimulating cell death and preventing metastasis. This review focuses on a complete overview of published reports that suggest chemopreventive action of wogonin and the mechanistic insights behind these neoplastic activities. It also emphasizes the synergistic improvements made by wogonin in chemoprevention. The factual data in this mini-review stimulate additional research on chemistry and toxicological profile of wogonin to confirm its safety issues. This review will encourage researchers to generalize the merits of wogonin to be used as potential compound for cancer treatment.

Genistein: a promising modulator of apoptosis and survival signaling in cancer.

Genistein, a commonly occurring isoflavone, has recently gained popularity owing to its ever-expanding spectrum of pharmacological benefits. In addition to health benefits such as improved bone health and reduced postmenopausal complications owing to its phytoestrogen properties, it has been widely evaluated for its anti-cancer potential. Several studies have established the potential for its usage in the management of breast, lung, and prostate cancers, and its usage has significantly evolved from early applications in traditional systems of medicine. This review offers an insight into its current status of usage, the chemistry, and pharmacokinetics of the molecule, an exploration of its apoptotic mechanisms in cancer management, and opportunities for synergism to improve therapeutic outcomes. In addition to this, the authors have presented an overview of recent clinical trials, to offer an understanding of contemporary studies and explore prospects for a greater number of focused trials, moving forward. Advancements in the application of nanotechnology as a strategy to improve safety and efficacy have also been highlighted, with a brief discussion of results from safety and toxicology studies.

In-Silico Design, Synthesis, and Pharmacological Evaluation of Oxadiazole-Based Selective Cyclo-oxygenase-2 Inhibitors.

A series of oxadiazole-based five-membered heterocyclic derivatives was designed and synthesized with the intent of exclusive cyclo-oxygenase-2 (COX-2) inhibition to acquire anti-inflammatory activity without the presence of gastric toxicity. Oxadiazole-based novel analogs were designed by using bioisosteric substitutions and were screened against the macromolecular target by using docking-based virtual screening to identify their potential inhibitors. These selective COX-2 inhibitors were further evaluated for their stability within the binding cavity of macromolecular complex by performing molecular dynamic simulation for 100 ns. Selected compounds were synthesized by using Naphthalene-2-yl-acetic acid as a starting material based on the fundamental structure of naphthalene. The naphthalene ring and methylene bridge of naphthalene-2-yl-acetic acid were retained in the rational molecular design by replacing the carboxyl group with biologically significant groups like 1,3,4-oxadiazoles, with the goal of obtaining a novel, superior, and relatively safe anti-inflammatory molecule with better efficacy and optimized pharmacokinetics. Anti-inflammatory as well as analgesic properties of the compounds were evaluated experimentally for their pharmacological efficiency.

Viral Loads in Skin Samples of Patients with Monkeypox Virus Infection: A Systematic Review and Meta-Analysis.

Despite monkeypox (mpox) being a public health emergency, there is limited knowledge about the risk of infectivity from skin viral loads during mpox infection. Thus, the aim of this study was to estimate cutaneous viral loads among mpox patients globally. Several databases, including Cochrane, EBSCOHost, EMBASE, ProQuest, PubMed, Scopus, and Web of Science, and preprint servers were searched concerning skin mpox viral loads in confirmed mpox subjects. In this systematic review and meta-analysis, a total of 331 articles were initially screened after the removal of duplicate entries. A total of nine articles were included in the systematic review and meta-analysis for the overall estimation of viral loads (Ct) using a random-effect model. The pooled cutaneous mpox viral load (lower Ct) was 21.71 (95% CI: 20.68-22.75) with a majority of positivity rates being 100%, highlighting a higher infectivity risk from skin lesions. The current results strongly support that skin mpox viral loads may be a dominant source of rapid transmission during current multi-national outbreaks. This important finding can help in constructing useful measures in relevant health policy.

Atypical Case of Highly Mutated h-TERT Promoter in Germline Genome from Buccal Mucosa Cancer.

Buccal mucosa cancer has an aggressive nature as it rapidly grows and penetrates with high recurrence rate. Strikingly, carcinoma of buccal mucosa is the most common cancer of oral cavity in India. Recently, telomerase and telomere biology have been implicated in the pathogenesis and progression in various cancers via regulation of telomere maintenance by telomerase expression which is controlled by telomerase reverse transcriptase (TERT) promoter. Strikingly, h-TERT promoter mutations have been incriminated in regulation of telomerase gene expression. Here, we present a 35 years old male with intense coughing, short breathlessness and fever since 15 days, was admitted to the pulmonary unit. He was a chronic smoker and gutka user. The cytopathological analysis of gastric aspirate revealed buccal mucosa carcinoma of IV stage. We identified h-TERT promoter mutations in isolated genomic DNA from whole blood using DNA sequencer. Genetic analysis disclosed that h-TERT promoter region was highly mutated in this patient. Identified mutations include C.-248 del G, C.-272 del G, C.-279 del G, C.-331 del G, C.-349 del G, C.-351 del C, C.-360 G > A, C.-362 T > A, C.-371 del T and C.-372 del T. Further, all identified mutations were subjected to predict the pathologic functional consequences using bioinformatics tools viz TFsitescan and CiiiDER which showed either loss or gain of transcription factors binding sites in h-TERT promoter. This is a unique case in which total 9 mutations were observed in h-TERT promoter in a single case. In conclusion, all together these mutations in h-TERT promoter may alter the epigenetics and subsequently the tenacity of binding transcription factors which are of functional significance.

Apoptotic and antimetastatic effect of cucurbitacins in cancer: recent trends and advancement.

The Cucurbitaceae family produces a class of secondary metabolites known as cucurbitacins. The eight cucurbitacin subunits are cucurbitacin B, D, E, I, IIa, L glucoside, Q, and R with the most significant anticancer activity. They are reported to inhibit cell proliferation, invasion, and migration; induce apoptosis; and encourage cell cycle arrest, as some of their modes of action. The JAK-STAT3, Wnt, PI3K/Akt, and MAPK signaling pathways, which are essential for the survival and apoptosis of cancer cells, have also been shown to be suppressed by cucurbitacins. The goal of the current study is to summarize potential molecular targets that cucurbitacins could inhibit in order to suppress various malignant processes. The review is noteworthy since it presents all putative molecular targets for cucurbitacins in cancer on a single podium.

Apoptotic Mechanisms of Quercetin in Liver Cancer: Recent Trends and Advancements.

Due to rising incidence rates of liver cancer and worries about the toxicity of current chemotherapeutic medicines, the hunt for further alternative methods to treat this malignancy has escalated. Compared to chemotherapy, quercetin, a flavonoid, is relatively less harmful to normal cells and is regarded as an excellent free-radical scavenger. Apoptotic cell death of cancer cells caused by quercetin has been demonstrated by many prior studies. It is present in many fruits, vegetables, and herbs. Quercetin targets apoptosis, by upregulating Bax, caspase-3, and p21 while downregulating Akt, PLK-1, cyclin-B1, cyclin-A, CDC-2, CDK-2, and Bcl-2. Additionally, it has been reported to increase STAT3 protein degradation in liver cancer cells while decreasing STAT3 activation. Quercetin has a potential future in chemoprevention, based on substantial research on its anticancer effects. The current review discusses quercetin's mechanisms of action, nanodelivery strategies, and other potential cellular effects in liver cancer.

Chemopreventive mechanisms of amentoflavone: recent trends and advancements.

In parallel to the continuous rise of new cancer cases all over the world, the interest of scientific community in natural anticancer agents has steadily been increased. In the past decades, numerous phytochemicals have been shown to possess a strong anticancer potential in preclinical conditions. One of such interesting compounds, derived from different plants such as ginkgo, hinoki, and St. John`s wort, is amentoflavone. In this review article, a wide range of anticancer properties of this natural biflavone are described, revealing its ability to suppress the malignant growth and lead tumor cells to apoptotic death, besides impeding also angiogenic and metastatic processes. Therefore, amentoflavone can be considered a potential lead compound for the development of novel anticancer drug candidates, definitely deserving further in vivo studies and also initiation of clinical trials. It is expected that this plant biflavone might be important, either alone or in combination with the current standard chemotherapeutics, in providing some alleviation for the continuous rise of global cancer burden.

Identification of h-TERT Promoter Mutations in Germline DNA from North Indian Lung Carcinoma Patients.

Lung cancer is a severe and the leading cause of cancer related deaths worldwide. The recurrent h-TERT promoter mutations have been implicated in various cancer types. Thus, the present study is extended to analyze h-TERT promoter mutations from the North Indian lung carcinoma patients. Total 20 histopathologically and clinically confirmed cases of lung cancer were enrolled in this study. The genomic DNA was extracted from venous blood and subjected to amplification using appropriate h-TERT promoter primers. Amplified PCR products were subjected for DNA Sanger sequencing for the identification of novel h-TERT mutations. Further, these identified h-TERT promoter mutations were analysed for the prediction of pathophysiological consequences using bioinformatics tools such as Tfsitescan and CIIDER. The average age of patients was 45 ± 8 years which was categorized in early onset of lung cancer with predominance of male patients by 5.6 fold. Interestingly, h-TERT promoter mutations were observed highly frequent in lung cancer. Identified mutations include c. G272A, c. T122A, c. C150A, c. 123 del C, c. C123T, c. G105A, c. 107 Ins A, c. 276 del C corresponding to -168 G>A, -18 T>A, -46 C>A, -19 del C, -19 C>T, -1 G>A, -3 Ins A, -172 del C respectively from the translation start site in the promoter of the telomerase reverse transcriptase gene which are the first time reported in germline genome from lung cancer. Strikingly, c. -18 T>A [C.T122A] was found the most prevalent variant with 75% frequency. Notwithstanding, other mutations viz c. -G168A [c. G272A] and c. -1 G>A [c. G105A] were found to be at 35% and 15% frequency respectively whilst the rest of the mutations were present at 10% and 5% frequency. Additionally, bioinformatics analysis revealed that these mutations can lead to either loss or gain of various transcription factor binding sites in the h-TERT promoter region. Henceforth, these mutations may play a pivotal role in h-TERT gene expression. Taken together, these identified novel promoter mutations may alter the epigenetics and subsequently various transcription factor binding sites which are of great functional significance. Thereby, it is plausible that these germline mutations may involve either as predisposing factor or direct participation in the pathophysiology of lung cancer through entangled molecular mechanisms.

An Appraisal on Synthetic and Medicinal Aspects of Fused Pyrimidines as Anti Neoplastic Agents.

Heterocyclic compounds are recognized to possess a high grade of structural diversity and a broad spectrum of therapeutic properties. About two-thirds of the New Chemical Entities approved by the FDA against cancer entail heterocyclic rings and are the foundation stone of medicinal chemistry. Pyrimidine being a major heterocyclic compound and a crucial base component of the genetic material, has emerged as the key structural component against cancer, the deadliest disease worldwide. Though many drugs are marketed against cancer, researchers are still investigating the more promising moieties against various malignancies due to the severity of this disease. In this review, an attempt has been made to assemble the reported literature of the previous five years on various synthetic procedures and the anti-cancer potential of various classes of fused pyrimidine analogs, which would help the researchers in designing new potent derivatives. Besides this, the review intends to focus on the comprehensive discussion on biological targets, modes of action, and structure-activity relationships of each class of fused pyrimidines as potential anticancer agents.

Computational Bioprospecting Guggulsterone against ADP Ribose Phosphatase of SARS-CoV-2.

Coronavirus Disease-2019 (COVID-19) is a highly contagious disease caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) classified the disease a as global public health hazard on 11 March 2020. Currently, there are no adequate measures to combat viral infections, including COVID-19, and the medication guidelines for the management of COVID-19 are dependent on previous findings from SARS-CoV and MERS-CoV research. Natural products have achieved widespread acceptance around the world as a means of enhancing healthcare and disease prevention. Plants are a potential source of antiviral factors such as flavonoids, phenolic acids, terpenoids, and others. Some of these agents exhibit a broad spectrum of antiviral activity. This study aimed to screen herbal leads for possible inhibitors of the SARS-CoV-2 ADP Ribose Phosphatase enzyme (ARP). Guggulsterone was found to be highly stabilized within the active site of the viral ARP enzyme by molecular dynamic simulation with very little fluctuation throughout the simulation timeframe of 100 ns. Thus, guggulsterone can be further used to develop a safe and competent medication for evolving therapy against SARS-CoV-2 in post-preclinical and clinical trials.