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Abstract: Discovery of MDM2 and MDM2-p53 interaction inhibitors changed the direction of anticancer research as it is involved in about 50% of cancer cases globally. Not only the inhibition of MDM2 but also its interaction with p53 proved to be an effective strategy in anticancer drug design and development. Various molecules of natural as well as synthetic origin have been reported to possess excellent MDM2 inhibitory potential. The present review discusses the pathophysiology of the MDM2-p53 interaction loop and MDM2/MDM2-p53 interaction inhibitors from literature covering recent patents. Focus has also been put on characteristic features of the active site of the target and its desired interactions with the currently FDA-approved inhibitor. The designing approach of previously reported MDM2/MDM2-p53 interaction inhibitors, their SAR studies, in silico studies, and the biological efficacy of various inhibitors from natural as well as synthetic origins are also elaborated. An attempt is made to cover recently patented MDM2/MDM2- p53 interaction inhibitors.

Background: The heterocyclic nucleus pyrimidine is present in several natural and synthetic chemical analogues and has proved its broad medicinal applications. Further, pyrimidine in the form of parent structure or basic skeleton of RNA and DNA is involved in controlling the immune functioning, and in turn, inflammatory reactions. Objective: The objective of the present study is to evaluate some novel pyrimidine analogues for antiinflammatory action. Method: Molecular docking studies of Indomethacin and selected analogues were carried out with the COX-2 enzyme (PDB: 4ZOL). The synthesis of derivatives of 4-Phenyl-6-(phenylamino)pyrimidine-2-ol derivatives was begun by following Perkin condensation between substituted acetanilides and substituted aromatic aldehydes to yield an intermediate, which in turn produces the required nucleus for treatment with urea. All synthesized compounds were evaluated for in vivo and in vitro anti-inflammatory activity. Result: The docking interaction reflects a good dock score when compared with indomethacin, a potent Anti-inflammatory drug. In the majority of the compounds, pyrimidine was able to form hydrogen bonding while the rest of the part was involved in hydrophobic bonding. All compounds were synthesized in good yield and confirmed by physical and spectral studies. In vitro studies showed that compounds 5a and 5e were better at controlling inflammation than the conventional treatment Antipyrine, while in vivo data showed that compounds 5a, 5c, 5e, and 5h were better at controlling inflammation than the standard drug Antipyrine. Conclusion: The compound with more than one electron releasing group on the aniline moiety of pyrimidine yields a decent result in the synthetic and experimental studies, but the absence of an electron withdrawing group favours stronger anti-inflammatory activity on the target.

Aim: Several new dihydropyridine-based calcium channel blockers have been synthesized and pharmacologically evaluated for the treatment of hypertension Background: Dihydropyridines constitute an important class of calcium channel blockers (CCBs) due to their high potency, wide heterogeneity and tremendous biological usefulness. As a follow-up to our previous studies on 4-aryl-1,4-dihydropyridines as calcium channel blockers for the treatment of hypertension, four new series of methyl ethyl ester substituted 1,4-dihydropyridines are reported. Objectives: The aim of the work was to study the effects of unsymmetrical ester substitutions on calcium channel blocking activity of dihydropyridines (DHPs) while retaining the aminoalkoxy side chain at various positions of the 4-aryl ring. The type and location of the substituents on the 4-aryl ring have been extensively explored to study the structure-activity relationship (SAR) in this series of dihydropyridines as calcium channel blockers. Methodology: The target DHPs were synthesized using modified Hantzsch condensation and further derivatization. The compounds were screened for their inhibitory potential against L-type calcium channels at a single concentration of 10 μM on NG108-15 cells (Neuroblastoma X Glioma). The most potent DHP 12 was also tested for its vasodilatory activity using rat thoracic aortic rings precontracted with KCl (30 mM) and in vivo antihypertensive activity in rats using the tail-cuff method. Results: The newly synthesized DHPs displayed diversified calcium channel blocking activity with compounds 1e, 1h, 2d, 2f, 2h, 6, 9, 11, 12 and 14, producing more than 50% inhibition of veratridine response. 3-imidazolylpropoxy substituted analogue 12 turned out to be the most potent compound of the four series of compounds and produced fairly higher inhibition (78.6%) of veratridine response in comparison to nifedipine (70%) at 10 μM. In addition, compound 12 produced potent vasodilatory and antihypertensive properties. Conclusion: Both location of the side chain and the type of substituent on methyl ethyl ester substituted 4-aryl ring affected the response of dihydropyridine derivatives towards L-type calcium channels.

Abstract: Vitamin K2 products were first applied to Japanese children, which can promote the growth of children's bones and eliminate their growing pain. At the same time, it does little harm to the human body, so it has attracted the attention of some scholars. Later, it was also proved to be effective in treating osteoporosis, especially for postmenopausal women. After years of research, some capabilities of VK2 have been discovered; it has been proved that it has great clinical value in treating osteoporosis, reducing intimal lipid deposition, diabetes, tumor, immune diseases, nervous system diseases and other diseases. There is no doubt that VK2 is an essential nutrient for human health, once vitamin K2 is deficient, it will cause a series of diseases. In recent years, some new evidences show that VK2 can also be used in leukemia and other diseases, which shows that VK2 still has great development potential. As a new adjuvant drug, VK2 has attracted worldwide attention and has been used in the clinic for many years. In this article, we mainly summarized the related research of VK2 in recent years, and expounded on several VK2-related signal pathways and the related mechanisms of these signal pathways in treating various diseases.

Abstract: Phenolic acids are now receiving a great deal of interest as pervasive human dietary constituents that have various therapeutic applications against chronic and age-related diseases. One such phenolic acid that is being utilized in traditional medicine is chlorogenic acid (CGA). It is one of the most readily available phytochemicals that can be isolated from the leaves and fruits of plants, such as coffee beans (Coffea arabica L.), apples (Malus spp.), artichoke (Cynara cardunculus L.), carrots (Daucus carota L.), betel (Piper betle L.), burdock (Arctium spp.), etc. Despite its low oral bioavailability (about 33%), CGA has drawn considerable attention due to its wide range of biological activities and numerous molecular targets. Several studies have reported that the antioxidant and anti-inflammatory potentials of CGA mainly account for its broad-spectrum pharmacological attributes. CGA has been implicated in exerting a beneficial role against dysbiosis by encouraging the growth of beneficial GUT microbes. At the biochemical level, its therapeutic action is mediated by free radical scavenging efficacy, modulation of glucose and lipid metabolism, down-regulation of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1β, and interferon-gamma (IFN-γ), upregulation of nuclear factor erythroid 2-related factor 2 (Nrf-2), and inhibition of the activity of nuclear factor- κβ (NF-κβ), thus helping in the management of diabetes, cardiovascular diseases, neurodegenerative disorders, cancer, hypertension etc. This review highlights the natural sources of CGA, its bioavailability, metabolism, pharmacotherapeutic potential, and underlying mechanisms of action for the clinical usefulness of CGA in the management of health disorders.

Objective: The purpose of this article is to describe the state-of-art of neuroanatomical and cellular aspects of the cerebellum in epilepsy. Background: Over the years, cerebellum epileptogenesis has been widely studied. There is growing evidence linking the cerebellum with this pathology by several other structures involved: mainly the limbic system, thalamus, cerebral cortex, red nucleus, and reticular formation. As a result, these anatomical and cellular changes in the cerebellum might trigger the genesis and propagation of seizures. Discussion: We herewith outline the cerebellum's deep nuclei physiological pathways, responsible for seizure spread via ion channels and neurotransmitter dysfunction. Additionally, we describe the shifts in seizures produced after cell death, gene expression, and protein interaction with their respective molecular and anatomical pathways. Conclusion: Finally, we highlight the role played by the cerebellum in seizure propagation to the brain and how it can be counteracted in some subtypes of drug-resistant epilepsy.

Abstract: We are experiencing a revolution in regenerative medicine. Recent developments in organoid technology have provided unique opportunities for studying human biology and diseases. Indeed, organoid models have revolutionized the in vitro culture tools for biomedical research by creating robust three-dimensional (3D) architecture to recapitulate the primary tissues' cellular heterogeneity, structure, and functions. Such organoid technology enables researchers to re-create human organs and diseases model in a culture dish. It thus holds excellent promises for many translational applications such as regenerative medicine, drug discovery, and precision medicine. This review summarizes the current knowledge on the progression and promotion of organoid models, particularly with the heart disease approach. We discuss the usefulness of clinical applications of cardiac organoids and ultimately highlight the currently advanced therapeutic strategies in vitro model of organoids aimed at personalizing heart disease treatment.

Abstract: Alzheimer’s Disease (AD) is a successive neurodegenerative disorder in the aged population. Many chemicals and phytochemicals are used to treat AD. Polyphenols which occur widely in various fruits, vegetables, beverages, and some other plant sources are gaining importance in AD treatment. Polyphenols comprise various subcategories, such as phenolic acids, lignans, tannins, stilbenes, hydroxybenzoic acid, hydroxycinnamic acid, and flavonoids. These compounds, as sole entities or in combination, can be used for treating AD because they have an abundance of antioxidants that are reported to be effective in free radical scavenging, metal ion chelating, and anti-inflammatory activities. Polyphenols of various plant origins have been studied, and these have been supported by in vitro assays and in vivo studies in rodents. These molecules protect neurons against oxidative stress and deposition of amyloid-β (Aβ) and tau proteins which play a vital role in the pathogenesis of AD. Consumption of wine and other foods rich in polyphenols has a beneficial effect on the neuronal signaling pathways, playing a vital role in shielding neuronal cells from neurodegeneration. Their ability to reduce free radicals and chelate metals are of great advantage. In this review, we highlight the various polyphenols that inhibit neuronal damage and progression of AD while also providing a cure. Some of the polyphenols covered are hesperidin, resveratrol, curcumin, catechin, kaempferol, and quercetin. The mechanisms of the actions of three polyphenols are also elaborated.

Background: Predicting drug-target interactions (DTIs) is an important topic of study in the field of drug discovery and development. Since DTI prediction in vitro studies is very expensive and time-consuming, computational techniques for predicting drug-target interactions have been introduced successfully to solve these problems and have received extensive attention. Objective: In this paper, we provided a summary of databases that are useful in DTI prediction and intend to concentrate on machine learning methods as a chemogenomic approach in drug discovery. Unlike previous surveys, we propose a comparative analytical framework based on the evaluation criteria. Methods: In our suggested framework, there are three stages to follow: First, we present a comprehensive categorization of machine learning-based techniques as a chemogenomic approach for drug-target interaction prediction problems; Second, to evaluate the proposed classification, several general criteria are provided; Third, unlike other surveys, according to the evaluation criteria introduced in the previous stage, a comparative analytical evaluation is performed for each approach. Results: This systematic research covers the earliest, most recent, and outstanding techniques in the DTI prediction problem and identifies the advantages and weaknesses of each approach separately. Additionally, it can be helpful in the effective selection and improvement of DTI prediction techniques, which is the main superiority of the proposed framework. Conclusion: This paper gives a thorough overview to serve as a guide and reference for other researchers by providing an analytical framework which can help to select, compare, and improve DTI prediction methods.

Background: Indole and its derivatives play an important role in the synthesis of commercially relevant intermediate molecules required for the synthesis of a wide range of bioactive molecules. Aim: Exploration of the synthesis of novel nonsteroidal anti-inflammatory drugs, as well as their computational studies and pharmacological effects, was aimed as an important component of the present research. Objective: the objective of present work was to synthesize some novel 1-(1H-indol-1-yl)ethanone compounds, analyse their computational effects on the COX-2 enzyme and to test their in vivo analgesic and anti-inflammatory activity. Method: The condensation of 4-(2-(1H-indol-1-yl)-2-oxoethoxy) benzaldehyde with substituted aniline in ethanol in the presence of a catalytic quantity of glacial acetic acid was performed, which yielded the new Indole derivatives. IR, NMR, mass spectroscopy and elemental analysis techniques were used to characterize the structures of new indole derivatives. To estimate the drug-like candidate’s nature, a number of molecular attributes of these derivatives were computed. The synthesized derivatives were docked with a specific reference cyclooxygenase-2 (COX-2) enzyme. The physical similarity of the newly synthesized derivatives (D1-D8) and indomethacin (the reference drug) was determined by evaluating seven physicochemical features by a software. Result: Although the bioavailability/drug likeness was found to be in the standard range, the synthesized compounds exhibited close similarity with those of the reference drug, and subsequent optimization was necessary. Conclusion: The newly synthesized indole derivatives as COX-2 inhibitors were evaluated for their biological properties, which included anti-inflammatory and analgesic efficacy Other: D-7 (1-(1H-indol-1-yl)-2-(4-((4-nitrophenyl)imino)methyl)phenoxy)ethanone) was found to have the strongest anti-inflammatory and analgesic activity amongst the eight target compounds.

Background: Tuberculosis is considered a global health problem; hence, the screening and synthesis of novel tuberculostatic drugs are a necessity. Molecular docking could drastically reduce the time of hit identification; however, initial validation is required to reduce the false-positive results. Objective: Assessment of several searching and scoring algorithms for a custom dataset of hydrazidehydrazone- based tuberculostatics was conducted to obtain a reliable docking protocol for future virtual screening. Methods: Modification in the scoring functions, size of the grid space, and presence of active waters of a GOLD 5.3 docking protocol was conducted. Subsequently, side-chain flexibility and ensemble docking were carried out to assess the role of protein flexibility in the correlation coefficient. In addition, docking simulations with Glide and free binding energy calculations with MM-GBSA were implemented. The Pearson correlation coefficient between the experimental and the acquired in silico data was calculated after each work step. The major interactions between the top-scored ligands and the active site of 2X22 were visualized applying Discovery Studio. Results: An optimized GOLD 5.3 docking protocol led to a drastically enhanced Pearson correlation coefficient of the training set, from 0.461 to 0.823, as well as an excellent pairwise correlation coefficient in the test set - 0,8405. Interestingly, the Glide docking scores and the free binding energy calculations with MM-GBSA did not achieve reliable results. During the visualization of the top-ranked compounds, it was observed that Lys165 played a major role in the formation of stable complexes. Conclusion: It could be concluded that the performance of the optimized GOLD 5.3 docking protocol demonstrated significantly higher reliability against the hydrazide-hydrazone dataset when compared to Glide docking simulations and MM-GBSA free binding energy calculations. The results could be utilized for future virtual screenings.

Purpose: To investigate the underlying mechanism of cardiomyocyte protection of carvedilol based on autophagy and apoptosis. Methods: Neonatal rat ventricular myocytes (NRVMs) were exposed to various concentrations of carvedilol before anoxia, and pretreated with 3-MA or compound C for inhibiting autophagy or p-AMPK expression. CCK-8 colorimeter and flow cytometry were used to determine the cell viability and apoptotic rates. The variation of mRNA and protein was measured by RT-PCR and Western blot. The presence of autophagosomes was observed by electron microscopy. Results: First, we found that carvedilol increased autophagic marker levels in a concentration-dependent manner and the number of autophagosomes in NRVMs. Moreover, carvedilol substantially enhanced the viability and noticeably reduced the CK, MDA and LDH levels and cell apoptosis rate compared with the anoxia group. In addition, carvedilol decreased the levels of caspase-3 and Bim in mRNA and protein, but such effect was blocked by the special autophagy inhibitor-3-MA, and the number of autophagosomes was significantly decreased when treated with 3-MA, indicating that carvedilol exhibited anti-apoptotic and anti-injury effects by inducing autophagy in anoxia NRVMs, but these effects can be abolished by adding 3-MA to suppress autophagy. Finally, the carvedilol treatment-induced autophagy by enhancing the activation of p-AMPK and inhibiting p-mTOR. Electron microscopy presented that the number of autophagosomes was significantly decreased when treating with compound C, indicating that carvedilol induced autophagy in anoxia NRVMs partly by the AMPK-mTOR signaling pathway. Conclusions: Carvedilol has cardioprotection by inducing autophagy against apoptosis partly through the AMPK/mTOR pathway during anoxia in NRVMs.

Abstract: COVID-19 is caused by SARS-CoV-2 and leads to acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and extrapulmonary manifestations in severely affected cases. However, most of the affected cases are mild or asymptomatic. Cannabinoids (CBs) such as tetrahydrocannabinol (THC) and cannabidiol (CBD), which act on G-protein-coupled receptors called CB1 and CB2, have anti-inflammatory effects. Many published studies show that CBs are effective in various inflammatory disorders, viral infections, and attenuation of ALI and ARDS. Therefore, the present narrative review aimed to summarize the possible immunological role of CBs in COVID-19. The effects of CBs are controversial, although they have beneficial effects via CB2 receptors and adverse effects via CB1 receptors against ALI, ARDS, and hyperinflammation, which are hallmarks of COVID-19. The present narrative review has shown that CBs effectively manage ALI and ARDS by suppressing pro-inflammatory cytokines, which are common in COVID-19. Therefore, CBs may be used to manage COVID-19 because of their potent anti-inflammatory effects, suppressing pro-inflammatory cytokines and inhibiting inflammatory signaling pathways.

Background: Pyrimidine and 1,2,4-triazole heterocycles have been linked to a variety of biological and pharmacological properties such as effective bactericides, fungicides, vermicides, insecticides, anticancer and antiviral agents. Accordingly, the synthetic derivatives and analogs of these molecules have attracted attention as potential pharmacological agents. Objective: A novel set of heterocyclic derivatives comprising 1,2,4-triazole, pyrimidine moieties was developed, synthesized, and assessed for their antimicrobial activity. Methods: In this study, we performed ligand-based pharmacophore modeling as a promising design strategy for the design of substituted triazolyl-pyrimidine derivatives as antitubercular agents. The designed compounds were synthesized and characterized by proton, carbon nuclear magnetic resonance spectroscopy, infrared, and mass spectroscopy. Synthesized compounds were screened for anti-TB activity using the agar micro dilution method against M. tuberculosis H37Rv strain. Results: Our results revealed that the target 1,2,4-triazoles 7d, 7e, 7c have potent potency against Gram- (+ve) bacteria S. epidermidis (MICs: 1.7, 3.7, 16.4 μg/mL), whereas final pyrimidines 7c, 7e, 7f, have the strongest antibacterial activity against Gram-(-ve) strain P. aeruginosa (MICs: 3.5, 6.4, 8.4 μg/mL). Among all tested compounds, 7a, 7e, and 7h revealed an outstanding antitubercular activity against M. tuberculosis H37RV strain with MICs of 3.24, 8.93, and 4.70 μg/mL, respectively. The most active ligand 7b reveals highest hydrophobic binding modes with ThrA:127 [2.194 A°], LysA:103 [3.103, 2.164 A°], GlyA:102 [1.713 A°], ArgA:238 [1.713 A°], ValA:101 [2.113 A°] (hydrogen bondings), AspA:129, GluA:201 [Pi-anion], AlaA:246, LeuA:180 [Pi-alkyl] and HisA:179 [3.104 A°] [Pi-Pi], respectively. Conclusion: In this communication, our aim has been verified by the synthesis of 3-methoxy-10,12- dimethyl-8-phenyl-6,7,8,12-tetrahydrobenzo[2,3]oxepino[4,5-d][1,2,4]triazolo[4,3-a] pyrimidine derivatives 7 in which 1,2,4-triazole and pyrimidine moieties with benzoxepine in a single molecular framework were found. After all the above findings, it can be concluded that these molecules become lead molecules for further synthetic and biological evaluation.

Abstract: Purine, one of the nucleotides, is an important substance for the metabolism and regulation of the body. Purine plays a key role not only in the composition of coenzymes but also in the supply of energy. Since purine was artificially synthesized, it has always been an important scaffold for respiratory diseases, cardiovascular diseases, and anti- tumor and anti-viral drugs. In addition to being widely used as competitive antagonists in the treatment of diseases, purines can be used in combination with other drugs and as precursors to benefit human life. Unfortunately, few new discoveries have been made in recent years. In this article, purine drugs in the market have been classified according to their different targets. In addition, their mechanism of action and structure-activity relationship have also been introduced. This paper provides details of the signaling pathways through which purine drugs can bind to the respective receptors on the surface of cells and cause consequent reactions within the cell, which finally affect the targeted diseases. The various receptors and biological reactions involved in the signaling for respective disease targets within the cells are discussed in detail.

Abstract: Systemic arterial hypertension (SAH) is a major risk factor for several secondary diseases, especially cardiovascular and renal conditions. SAH has a high prevalence worldwide, and its precise and early recognition is important to prevent the development of secondary outcomes. In this field, the study of biomarkers represents an important approach to diagnosing and predicting the disease and its associated conditions. The use of biomarkers in hypertension and hypertension-related disorders, such as ischemic stroke, intracerebral hemorrhage, transient ischemic attack, acute myocardial infarction, angina pectoris and chronic kidney disease, are discussed in this review. Establishing a potential pool of biomarkers may contribute to a non-invasive and improved approach for their diagnosis, prognosis, risk assessment, therapy management and pharmacological responses to a therapeutic intervention to improve patients' quality of life and prevent unfavorable outcomes.

Background: In the current Alzheimer’s disease therapy as the preferred treatment are applied acetylcholinesterase inhibitors. Aiming to identify the active pharmacophores necessary for increased acetylcholinesterase inhibitory activity, some docking studies have been applied. Methods: In silico docking evaluation of the binding modes, identification of acetylcholinesterase inhibitory activity in vitro through Ellman’s test and ITC protocol, and the in vivo effect. PAMPA evaluation of the GIT and BBB permeability. Results: In the present study, two series previously synthesized in our laboratory, arylpiperazine derivatives of theobromine were docked into the rhAChE active sites. Ellman’s test outlined molecules LA1 and LA7 as the most active, with IC50 of 0.708 and 0.299 μM, respectively. In the acute toxicity test, LA7 given intraperitoneally in mice showed moderate toxicity with LD50 of 87.5 mg/kg. The new compound, administered i.p. for 12 days at doses 2 mg/kg/day and 4 mg/kg/day, respectively, showed a pronounced acetylcholinesterase inhibitory activity in vivo. Conclusion: The corresponding binding modes were identified, where the docking pose for the studied molecules depends on the protonated state of the nitrogen atom of the piperazine moiety. In the best scored pose for LA7, the xanthine moiety is bound into the catalytic active site (CAS) of acetylcholinesterase, while the arylpiperazine fragment is placed into the peripheral binding site (PAS). For the evaluated selected structures, good permeability through the GIT and BBB assessed by PAMPA was also determined.

Aims: This study documented hepatic tissue's protective activity against oxidative damage mediated experimental models of breast cancer. Background: Gaviola has a long history of improving the protection mechanism against many diseases as an antioxidant and anticancer dietary agent. Objective: The purpose of this study is to establish changes in hepatic profiling, antioxidants, inflammatory cytokine expression, and DMBA-induced hepatic histopathology of mammalian rats. Method: 7,12-dimethylbenz[a] anthracene (DMBA), PAHs, used orally in female Sprague Dawley rats Fifty-seven days-old with breast cancer single-dose diluted in sesame oil of 20 mg/kg/body weight. The cancer-bearing animals had 45 days gastrogavagated at 200 mg/kg/body weight with Graviola. The serum samples were taken at the end of the experiment. The rats were sacrificed to establish the hepatic protective activity of the Graviola by testing hepatic and oxidative stress markers. Result: Graviola therapy shows that enzymatic and non-enzymatic antioxidants and lipid peroxide levels have increased efficiency and have restored the high activity of hepatic marker enzymes such as ALT, AST, ALP, and GGT. To date, hepatic expression of nuclear factor erythroid 2-like 2 (Nfe2l2) and nuclear factor kappa B subunit 1 (Nfkb1) mediated rats have normalized. In addition, histological observations have demonstrated that Graviola's treatment effectively protects the liver from the oxidative damage caused by DMBA, reinforcing its hepatic defensive nature. Conclusion: Graviola therapy improves the efficiency of both enzymatic and non-enzymatic antioxidants and lipid peroxide levels. It also helps in the restoration of other liver enzymes.

Background: Plants have played an essential role in the search for new compounds for the most diverse therapeutic purposes. Recently, more attention has been paid to natural antioxidants because of the possible insecurity of synthetic antioxidants. Objective: The review is aimed at summarizing the most important and common natural antioxidants and their resources from medicinal plants. Method: The research was performed using data bases of PubMed, Google Scholar, Science Direct, Taylor and Francis, etc. to search for all collected scientific publications. Results: The most important medicinal plants with antioxidant activities in Iran are Artemisia, berberry fruit, borage, calendula, coriander, cumin, green tea, hawthorn, jujube, pomegranate, rose, rosemary, black zira, tea, and thyme. Important traditional medicinal plants with antioxidant activities in China are Asparagus, bindii, blueberries, camellia, Chinese bayberry, Chinese bitter melon, Chinese cabbage, Chinese cherry, Chinese jujube, Chinese olive, pomegranate, Chinese rose tea, Chinese toon, Chinese watermelon, black tea, knotweed, Chinese quince, Chinese rhubarb, sumac, wolfberry, dendrobium, drumstick tree, Fiscus species, ginger, ginkgo, goji berry, grape, Jerusalem thorn, kiwifruit seed oil, and liquorice root. Anacardium occidentale L., Ananas comosus (L.) Merril, Baccharis trimera (Less) DC., Carapa guianensis Aubl., Casearia sylvestris Sw., Cordia verbenacea DC., Croton lechleri Müll. Arg., and Eugenia uniflora L. are the main medicinal plants with antioxidant activities in Brazil. Conclusion: Antioxidants are those molecules that are involved in the scavenging of these reactive species causing oxidative stress and are defined as those substances which could prevent the oxidation of the substrate at low concentrations. The main derived exogenous natural antioxidants are derived from medicinal plants, fruits, foods, flowers, and traditional herbal medicines in different parts of the world

Background: Statins are the main lipid-lowering drugs and are used in the prevention of cardiovascular diseases (CVDs). Since the results have been, to some extent, inconsistent in the clinical trials concerning different types of CVDs, a systematic review and meta-analysis was performed to prove the effect of statins on decreasing elevated levels of total cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in patients with CVDs. Methods: Literature search was performed on major electronic databases (MEDLINE/ PubMed, Scopus, and ISI Web of Science) from inception up to July 2021 to find randomized controlled trials (RCTs) evaluating the effect of different statins on different types of CVDs. The effect size was determined using weighted mean difference (WMD) and corresponding 95% confidence interval (CI). Results: Statin therapy significantly decreased levels of total cholesterol (WMD = -33.37 mg/dl, 95% CI: -45.98 to -20.76, P Conclusion: Statin therapy was found effective in lowering levels of total cholesterol, LDL-C, and TG, and increasing levels of HDL-C in patients with different CVDs.

Background: The rapidly widespread SARS-CoV-2 infection has affected millions worldwide, thus becoming a global health emergency. Although vaccines are already available, there are still new COVID-19 cases daily worldwide, mainly due to low immunization coverage and the advent of new strains. Therefore, there is an utmost need for the discovery of lead compounds to treat COVID-19. Objective: Considering the relevance of the SARS-CoV-2 MPRO in viral replication and the role of the isoquinoline moiety as a core part of several biologically relevant compounds, this study aimed to identify isoquinoline-based molecules as new drug-like compounds, aiming to develop an effective coronavirus inhibitor. Methods: 274 isoquinoline derivatives were submitted to molecular docking interactions with SARS-CoV-2 MPRO (PDB ID: 7L0D) and drug-likeness analysis. The five best-docked isoquinoline derivatives that did not violate any of Lipinski’s or Veber’s parameters were submitted to ADMET analysis and molecular dynamics (MD) simulations. Results: The selected compounds exhibited docking scores similar to or better than chloroquine and other isoquinolines previously reported. The fact that the compounds interact with residues that are pivotal for the enzyme's catalytic activity, and show the potential to be orally administered makes them promising drugs for treating COVID-19. Conclusion: Ultimately, MD simulation was performed to verify ligand-protein complex stability during the simulation period.

Background: Amphotericin B is a gold-standard drug, particularly for the treatment of systemic fungal infections. However, its low solubility and permeability limit its application. To improve its bioavailability, AmB may be conjugated with various water-soluble auxiliary groups. Methods: Custom R group Enumeration was used at the designated sites of Amphotericin B. The designated sites taken into consideration are the carboxyl moiety of the aglycone part and the amine moiety of the glycone part of Amphotericin B for Enumeration purposes. The enumerated molecules were subjected to QikProp properties. Results: We identified fourteen hits with improved predicted aqueous solubility and cell permeability. Conclusion: Enumeration might be applicable in improving bioavailability, which could lead to the oral formulation of the Amphotericin B drug.

Abstract: Obesity, as an unfavorable consequence of our modern lifestyle, can promote the emergence of other disorders, like diabetes and cardiovascular disease, that negatively impact quality of life. Therefore, prevention and treatment of obesity and its related comorbidities are critical. Lifestyle modification is the first and most important step but, in practical terms, presents a major challenge to many patients. So, the development of new strategies and therapies is critical for these patients. Although herbal bioactive compounds have recently gained attention for their ability to prevent and treat conditions related to obesity, no ideal pharmacological treatment has been found to treat obesity. Curcumin, one of the compounds extracted from turmeric, is a well-studied active herbal extract; however, its poor bioavailability and solubility in water, instability against temperature, light and pH fluctuations and rapid excretion limit its therapeutic application. Curcumin modification can, however, provide novel analogues with better performance and fewer disadvantages in comparison to the original structure. In the past few years, the positive effects of synthetic analogues of curcumin for the treatment of obesity, diabetes and cardiovascular disorders have been reported. In this review, we evaluate the strengths and weaknesses of the reported artificial derivatives and assess their practicality as therapeutic agents.

Background: Cancer is a complex disease in which some of the cells grow uncontrollably and spread to other parts of the body. Objective: The present study focuses on molecular docking and synthesis of novel flavone derivatives substituted with heterocyclic rings. Objective: The present study focuses on molecular docking and synthesis of novel flavone derivatives substituted with heterocyclic rings. Methods: The anticancer activity of novel flavones against human aromatase enzyme using human breast cancer cell line MCF-7 through MTT assay was demonstrated. The synthesized compounds for the determination of single or double-strand DNA damage through the single-cell electrophoresis/comet assay were evaluated. Results: In this study, we found that the derivative 3M with Morpholine ring showed the highest anticancer potency against the MCF-7 cell line compared to that of other flavone derivatives. Compound 3T showed less cytotoxicity against the MCF-7 cell line. Conclusion: Based on the findings, flavone scaffolds can be selected as a skeleton for the development of heterocyclic amine-containing flavones with the potential to develop as anticancer drugs.

Abstract: Epilepsy is a chronic neurological disorder characterized by periodic and unpredictable seizures affecting the neurobiological, psychological, cognitive, economic, and social well-being of patients. It is one of the causes of concern in developed as well as developing countries as currently marketed drugs are not capable of providing protection against it. Although several heterocyclic moieties have been frequently used as building blocks for the preparation of anticonvulsant drugs, more focused and consistent research on the synthesis of potential molecules with less adverse effects is the need of the hour. It can be concluded on the basis of available research reports that among several heterocyclic compounds, benzo-fused five-membered heterocyclic moieties (benzothiazole and benzimidazole) have been utilized far less than their great potential as building blocks for the synthesis of anticonvulsant drugs. Various reports clearly established that the required pharmacophore model could be easily achieved through benzothiazole and benzimidazole moieties as two hetero atoms and aryl rings are present in the structure. The present study highlights various synthetic approaches for anticonvulsant benzothiazole and benzimidazole derivatives with their structure-activity relationship studies in order to provide a trove of knowledge to medicinal chemists for future research.

Abstract: Reactive species (RS) are produced in aerobic and anaerobic cells at different concentrations and exposure times, which may trigger diverse responses depending on the cellular antioxidant potential and defensive devices. Study searches were carried out using the PubMed database of the National Library of Medicine-National Institutes of Health. Cellular RS include reactive oxygen (ROS), nitrogen (RNS), lipid (RLS) and electrophilic species that determine either cell homeostasis or dysfunctional biomolecules. The complexity of redox signalling is associated with the variety of RS produced, the reactivity of the target biomolecules with RS, the multiplicity of the counteracting processes available, and the exposure time. The continuous distortion in the prooxidant/ antioxidant balance favoring the former is defined as oxidative stress, whose intensity determines (i) the basal not harmful unbalance (oxidative eustress) at RS levels in the pM to nM range that supports physiological processes (e.g., immune function, thyroid function, insulin action) and beneficial responses to external interventions via redox signalling; or (ii) the excessive, toxic distortion (oxidative distress) at RS levels exceeding those in the oxidative eustress zone, leading to the unspecific oxidation of biomolecules and loss of their functions causing cell death with associated pathological states. The cellular redox imbalance is a complex phenomenon whose underlying mechanisms are beginning to be understood, although how RS initiates cell signalling is a matter of debate. Knowledge of this aspect will provide a better understanding of how RS triggers the pathogenesis and progression of the disease and uncover future therapeutic measures.

Background: Peritoneal adhesions (PA) are a common complication of abdominal operations. Previous studies indicate that inhibition of inflammation and fibrosis at sites of peritoneal damage may prevent the development of intra-abdominal adhesions. Zingiber officinalis Roscoe (ginger) and Panax ginseng (P. ginseng) are herbal products with antioxidant and anti-inflammatory effects that can have restorative properties. Objective: This research aimed to examine the impact of ginger and p. ginseng on prevention of PA in a rat model after surgery. Methods: Following a laparotomy, the wall of the cecum was rubbed to induce intra-abdominal adherence in Wistar rats. Ginger (400mg/kg) and P. ginseng (500mg/kg) were orally adminstered to the animals. The animals were sacrificed on the 10th day after surgery, and the Nair and Leach scoring system was used to assess adhesion. The microscopic histology of the induced cecal adhesions was evaluated. An enzyme-linked immunosorbent assay (ELISA) was used to determined tissue levels of transforming growth factor-beta (TGF-β) on homogenized PA tissue. Real-time PCR was performed to quantify the mRNA expression of IL-1β, TNF-α, Col 1a1, and Col 3a1 in rat tissue. Result: The adhesion score and histopathological rating based on the Nair and Leach scoring criteria showed lower adhesion scores in the group of rats treated with P. ginseng compared to the control group (p Conclusion: The study's outcome recommends that P. ginseng could be an effective agent for preventing the PA and inflammation during the post-operative stage.

Aim: To provide new methods and ideas for the clinical application of integrated traditional Chinese and Western medicine in the treatment of esophageal cancer. Background: Traditional Chinese medicine compound Kushen injection (CKI) has been widely used in the clinic with adjuvant radiotherapy and chemotherapy. However, the mechanism of action of CKI as adjuvant therapy for esophageal cancer has not yet been described. Method: This study is based on network pharmacology, data mining, and molecular docking technology to explore the mechanism of action of CKI in the treatment of esophageal cancer. We obtained the effective ingredients and targets of CKI from the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) and esophageal cancer-related genes from the Online Mendelian Inheritance in Man (OMIM) and GeneCards databases. Result: CKI mainly contains 58 active components. Among them, the top 5 active ingredients are quercetin, luteolin, naringenin, formononetin, and beta-sitostero. The target protein of the active ingredient was matched with the genes associated with esophageal cancer. The active ingredients targeted 187 esophageal cancer target proteins, including AKT1, MAPK1, MAPK3, TP53, HSP90AA1, and other proteins. Then, we enriched and analyzed the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and used AutoDockVina to dock the core targets and compounds. Finally, PyMOL and Ligplot were used for data visualization. Conclusion: This study provides a new method and ideas for the clinical application of integrated traditional Chinese and Western medicine in the treatment of esophageal cancer.

Abstract: Enzymes are highly specific catalysts that accelerate reactions in biological systems. Carbonic anhydrase (CA) is an enzyme found in plants, microorganisms, and vertebrates. CA catalyses CO2 hydration/ dehydration. There are different families and isoenzymes of CAs. Fifteen α-CA isoenzymes have been reported in humans. The status of CO2 hydration and dehydration is important for a variety of biological processes. CAs play an important role in many physiological and pathological events in several tissue types. Their levels are increased in some diseases; therefore, CA inhibition has been applied as a therapeutic option. However, the high diversity of these isoenzymes is an important consideration. Isoenzyme- specific CA inhibitors can reduce the side effects of treatment. Some agents containing additional sulfonamides approved for other therapeutic applications, such as topiramate, celecoxib/valdecoxib, sulpiride, and famotidine, have inhibitory effects on CA isoenzymes. These bind to the zinc ion in the CA active site. Recently, research has been conducted on the use of a hybrid form of active ingredient and a CA inhibitor. CA inhibitor-NSAID hybrid compounds demonstrated more efficacy than NSAIDs in arthritis, which has attracted further attention of researchers in conducting research on CA-hybrid drugs.

Abstract: Metastases result from a complicated process in which malignant cells detach from the initial cancerous cells and disseminate to other locations. Few therapy options are available that aim to prevent or counteract metastatic disorders. Identifying novel molecular targets and medications, developing techniques to distribute preexisting chemicals, and combining resources to supervise individualized treatment are all part of this process. Because of its improved sensitivity, accuracy, and multiplexed measurement capacity, nanotechnology has been investigated to recognize extracellular cancer biomarkers, cancer cells, and bioimaging. Nanotechnology is a vast and rapidly expanding field with enormous potential in cancer treatment. Nanoparticles can treat resistant cancers with minimal harm to healthy tissues and organs by targeting cancer stem cells. Nanoparticles can also trigger immune cells, which can help to destroy malignancies. The potential of herbal-based nano formulation as a specialized and high-efficacy therapeutic method opens the path for future research into the screening and use of herbal nanoparticles for cancer treatment. The possible impacts of nanoparticles in the therapy of metastatic cancer, specifically on cell stability, proliferation suppression, eventual interaction with adhesion molecules, and antiangiogenic activity, are discussed in this paper.