Chemical characterization, neuroprotective effect, and evaluation of the petroleum ether extract of three palm tree species against glutamate-induced excitotoxicity in rats.

The burden of neurological disorders is growing substantially with limited therapeutic options, urging the consideration and assessment of alternative strategies. In this regard, we aimed to elucidate the phytochemical profile of the petroleum ether extract (PEE) of three palm tree species: Burret, H. Wendl.

Novel pyrimidine derivatives and black cumin as xanthine oxidase inhibitors: Synthesis, docking study and formulation.

In this work, to attempt discovery of novel xanthine oxidase (XO) inhibitors, we developed a method for optimizing the Nigella sativa oil extraction by considering the seed size particles, the liquid seed ratio, the duration of the extraction procedure and the temperature of extraction. On the other hand, new pyrimidine and triazolopyrimidine derivatives were prepared in an attempt to mimic the pyrazolpyrimidine structure of allopurinol (a well-known xanthine oxidase inhibitor drug). Most of the developed compounds were shown to have strong xanthine oxidase inhibitory activities, while Nigella sative extract and compound 6b ranked as the most effective inhibitors (IC=1.

Design, synthesis, molecular modeling, in vitro and in vivo biological evaluation of potent anthranilamide derivatives as dual P-glycoprotein and CYP3A4 inhibitors.

Paclitaxel (PTX) is considered the blockbuster chemotherapy treatment for cancer. Paclitaxel's (PTX) oral administration has proven to be extremely difficult, mostly because of its susceptibility to intestinal P-glycoprotein (P-gp) and cytochrome P450 (CYP3A4). The concurrent local inhibition of intestinal P-gp and CYP3A4 is a promising approach to improve the oral bioavailability of paclitaxel while avoiding potential unfavorable side effects of their systemic inhibition.

Neuroprotective activity of (L.) Schott leaves against monosodium glutamate-induced excitotoxicity in rats: phytochemical and molecular docking study.

(L.) Schott is a food crop with long history of use in treatment of various disorders including neurological diseases. The methanolic leaves extract (ME) and its -butanol fraction (-BF) demonstrated significant neuroprotective activity in monosodium glutamate induced excitotoxicity in rats.

Droplet digital polymerase chain reaction detection of KRAS mutations in pancreatic FNA samples: Technical and practical aspects for routine clinical implementation.

Background: Pancreatic adenocarcinoma (PDAC) is associated with a 5-year survival rate of less than 6%, and current treatments have limited efficacy. The diagnosis of PDAC is mainly based on a cytologic analysis of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) samples. However, the collected specimens may prove noncontributory in a significant number of cases, delaying patient management and treatment.

Investigating the Association between Sociodemographic Factors and Chronic Disease Risk in Adults Aged 50 and above in the Hungarian Population.

Chronic diseases are a major cause of mortality and morbidity globally, with non-communicable diseases being responsible for most deaths. Older adults are at a higher risk of developing chronic diseases due to various sociodemographic and lifestyle factors such as age, sex, income, education, employment, place of residence, dietary supplementation, tobacco use, and alcohol consumption. Understanding the relationship between these factors and chronic diseases is crucial for identifying vulnerable populations and improving healthcare delivery.

Antimicrobial, antiproliferative activities and molecular docking of metabolites from Alternaria alternata.

Endophytic fungi allied to plants have sparked substantial promise in discovering new bioactive compounds. In this study, propagation of the endophytic fungus Alternaria alternata HE11 obtained from Colocasia esculanta leaves led to the isolation of Ergosterol (1), β-Sitosterol (2), Ergosterol peroxide (3), in addition to three dimeric naphtho-γ-pyrones, namely Fonsecinone A (4), Asperpyrone C (5), and Asperpyrone B (6), which were isolated from genus Alternaria for the first time. Structures of the isolated compounds were established on the basis of extensive 1D and 2D NMR and, MS measurements.

Novel benzo chromene derivatives: design, synthesis, molecular docking, cell cycle arrest, and apoptosis induction in human acute myeloid leukemia HL-60 cells.

A series of benzo[]chromenes, benzo[]chromenes, and benzo[]chromeno[2,3-]pyrimidines were prepared. All the newly synthesised compounds were selected by National Cancer Institute for single-dose testing against 60 cell lines. Benzo[]chromenes and showed promising anti-cancer activity and selected for the five-dose testing.

Novel pyrrolopyrimidine derivatives: design, synthesis, molecular docking, molecular simulations and biological evaluations as antioxidant and anti-inflammatory agents.

Current medical approaches to control the Covid-19 pandemic are either to directly target the SARS-CoV-2 innovate a defined drug and a safe vaccine or indirectly target the medical complications of the virus. One of the indirect strategies for fighting this virus has been mainly dependent on using anti-inflammatory drugs to control cytokines storm responsible for severe health complications. We revealed the discovery of novel fused pyrrolopyrimidine derivatives as promising antioxidant and anti-inflammatory agents.

Synthesis Strategies and Medicinal Value of Pyrrole and its Fused Heterocyclic Compounds.

In the last several decades, interest in pyrrole and pyrrolopyrimidine derivatives has increased owing to their biological importance, such as anti-tumor, anti-microbial, anti-inflammatory, anti-diabetic, anti-histaminic, anti-malarial, anti-Parkinson, antioxidant and anti-viral effects, specially recently against COVID-19. These tremendous biological features have motivated scientists to discover more pyrrole and fused pyrrole derivatives, owing to the great importance of the pyrrole nucleus as a pharmacophore in many drugs, and motivated us to present this article, highlighting on the different synthetic pathways of pyrrole and its fused compounds, specially pyrrolopyrimidine, as well as their medicinal value from 2017 till 2021.

Synthesis of novel calcium channel blockers with ACE2 inhibition and dual antihypertensive/anti-inflammatory effects: A possible therapeutic tool for COVID-19.

Hypertension has been recognized as one of the most frequent comorbidities and risk factors for the seriousness and adverse consequences in COVID-19 patients. 3,4-dihydropyrimidin-2(1H) ones have attracted researchers to be synthesized via Beginilli reaction and evaluate their antihypertensive activities as bioisosteres of nifedipine a well-known calcium channel blocker. In this study, we report synthesis of some bioisosteres of pyrimidines as novel CCBs with potential ACE2 inhibitory effect as antihypertensive agents with protective effect against COVID-19 infection by suppression of ACE2 binding to SARS-CoV-2 Spike RBD.

Synthesis and Evaluation of Some Uracil Nucleosides as Promising Anti-Herpes Simplex Virus 1 Agents.

Since herpes simplex virus type 1 (HSV-1) infection is so widespread, several antiviral drugs have been developed to treat it, among which are uracil nucleosides. However, there are major problems with the current medications such as severe side-effects and drug resistance. Here we present some newly synthesized cyclic and acyclic uracil nucleosides that showed very promising activity against HSV-1 compared to acyclovir.

[Impact of algorithms proposed by the Cutaneous Lymphoma French Study Group for diagnosis of cutaneous lymphoproliferations].

After a first diagnosis proposition, management of cutaneous lymphomas requires a systematic review by an expert pathologist and each case is presented to a multidisciplinary meeting in the setting of the French Study Group of Cutaneous Lymphomas to propose an adequate treatment. A retrospective study of the 2760 cutaneous lymphoproliferations retrieved between 2010 and 2011 were analyzed and demonstrated the interest of diagnostic algorithms we built with the group. The objective of our study was to compare two cohorts from 2010-2011 and 2015-2017 regarding the proportion of cases sent for validation or expertise, the concordance and mismatch rates and potential diagnostic issues using our diagnostic algorithms.

Molecular modelling insights into a physiologically favourable approach to eicosanoid biosynthesis inhibition through novel thieno[2,3-b]pyridine derivatives.

In this research, we exploited derivatives of thieno[2,3-b]pyridine as dual inhibitors of the key enzymes in eicosanoid biosynthesis, cyclooxygenase (COX, subtypes 1 and 2) and 5-lipoxygensase (5-LOX). Testing these compounds in a rat paw oedema model revealed potency higher than ibuprofen. The most active compounds 7a, 7b, 8b, and 8c were screened against COX-1/2 and 5-LOX enzymes.

Allosteric HIV-1 integrase inhibitors promote aberrant protein multimerization by directly mediating inter-subunit interactions: Structural and thermodynamic modeling studies.

Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) bind at the dimer interface of the IN catalytic core domain (CCD), and potently inhibit HIV-1 by promoting aberrant, higher-order IN multimerization. Little is known about the structural organization of the inhibitor-induced IN multimers and important questions regarding how ALLINIs promote aberrant IN multimerization remain to be answered. On the basis of physical chemistry principles and from our analysis of experimental information, we propose that inhibitor-induced multimerization is mediated by ALLINIs directly promoting inter-subunit interactions between the CCD dimer and a C-terminal domain (CTD) of another IN dimer.

Indole-based allosteric inhibitors of HIV-1 integrase.

Employing a scaffold hopping approach, a series of allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) have been synthesized based on an indole scaffold. These compounds incorporate the key elements utilized in quinoline-based ALLINIs for binding to the IN dimer interface at the principal LEDGF/p75 binding pocket. The most potent of these compounds displayed good activity in the LEDGF/p75 dependent integration assay (IC50=4.