New 6-nitro-4-substituted quinazoline derivatives targeting epidermal growth factor receptor: design, synthesis and anticancer studies.

Twenty compounds of 6-nitro-4-substituted quinazolines were synthesized. The new derivatives were evaluated for their epidermal growth factor receptor (EGFR) inhibitory activity. The most potent derivatives were assessed for their cytotoxicity against colon cancer and lung cancer cells, in addition to normal fibroblast cells.

In Silico and In Vitro Screening of Some Pregnane Glycosides Isolated from Certain Caralluma Species as SARS-COV-2 Main Protease Inhibitors.

SARS-CoV-2 caused pandemic represented a major risk for the worldwide human health, animal health and economy, forcing extraordinary efforts to discover drugs for its prevention and cure. Considering the extensive interest in the pregnane glycosides because of their diverse structures and excellent biological activities, we investigated them as antiviral agents against SARS-COV-2. We selected 21 pregnane glycosides previously isolated from the genus Caralluma from Asclepiadaceae family to be tested through virtual screening molecular docking simulations for their potential inhibition of SARS-CoV-2 M.

Design, synthesis and anticancer evaluation of some novel 7-hydroxy-4-methyl-3-substituted benzopyran-2-one derivatives.

22 derivatives of 7-hydroxy-4-methyl-3-substituted benzopyran-2-one were designed, synthesized and evaluated for their anticancer activity. The prepared compounds were screened for their cytotoxicity against the MCF-7 breast cancer cell line. The best five were then evaluated against MCF10a to check their safety and then tested for their PI3K and Akt-1 inhibitory action.

A multidisciplinary approach to the antioxidant and hepatoprotective activities of Pampan fruit; and biological evaluations, and investigations.

The Libyan Strawberry, Pampan (ARB), is an endemic Jebel Akhdar plant used for traditional medicine. This study presents the antioxidant and hepatoprotective properties of ARB fruit-extract. ARB phytochemical analysis indicated the presence of 354.

Novel indolinone-tethered benzothiophenes as anti-tubercular agents against MDR/XDR M. tuberculosis: Design, synthesis, biological evaluation and in vivo pharmacokinetic study.

Joining the global effort to eradicate tuberculosis, one of the deadliest infectious killers in the world, we disclose in this paper the design and synthesis of new indolinone-tethered benzothiophene hybrids 6a-i and 7a-i as potential anti-tubercular agents. The MICs were determined in vitro for the synthesized compounds against the sensitive M. tuberculosis strain ATCC 25177.

An innovative combination of Box-Behnken design and ecofriendly approaches for the simultaneous determination of aspirin, clopidogrel, atorvastatin and rosuvastatin in their fixed-dose combination tablets.

Three-levels Box-Behnken design was used in the experimental design approach for the optimization of chromatographic parameters to achieve the optimum resolution and sharp peak shape within a reasonable run time. A method that is sensitive, reliable, and selective was constructed and validated for the simultaneous measurement of a combination therapy that contains blood-thinning and cholesterol-lowering compounds. The four cited drugs namely, aspirin (ASP), clopidogrel (CLP), atorvastatin (ATV) and rosuvastatin (ROS) were estimated in bulk and in pharmaceutical dosage forms in line with International Council for Harmonization guidelines.

Rumex vesicarius L. boosts the effectiveness of sorafenib in triple-negative breast cancer by downregulating BCl2, mTOR, and JNK, and upregulating p21 expression.

Background/aim: Triple-negative breast cancer (TNBC) is characterized by poor prognosis, rapid progression, serious clinical behavior, an elevated risk of metastasis, and resistance to standard treatments. Traditional medicine practitioners value Rumex vesicarius L. (RMV) for a variety of reasons, including the plant's antioxidant capabilities.

Discovery of pyrimidine-tethered benzothiazole derivatives as novel anti-tubercular agents towards multi- and extensively drug resistant .

In this study, new benzothiazole-pyrimidine hybrids (-, , -, and -) were designed and synthesised. Two different functionalities on the pyrimidine moiety of lead compound were subjected to a variety of chemical changes with the goal of creating various functionalities and cyclisation to further elucidate the target structures. The potency of the new molecules was tested against different tuberculosis (TB) strains.

Identification of sulphonamide-tethered -((triazol-4-yl)methyl)isatin derivatives as inhibitors of SARS-CoV-2 main protease.

SARS-CoV-2 pandemic in the end of 2019 led to profound consequences on global health and economy. Till producing successful vaccination strategies, the healthcare sectors suffered from the lack of effective therapeutic agents that could control the spread of infection. Thus, academia and the pharmaceutical sector prioritise SARS-CoV-2 antiviral drug discovery.

Synergistic antiviral activity of Lactobacillus acidophilus and Glycyrrhiza glabra against Herpes Simplex-1 Virus (HSV-1) and Vesicular Stomatitis Virus (VSV): experimental and In Silico insights.

Background: The emergence of different viral infections calls for the development of new, effective, and safe antiviral drugs. Glycyrrhiza glabra is a well-known herbal remedy possessing antiviral properties.

Objective: The objective of our research was to evaluate the effectiveness of a newly developed combination of the probiotics Lactobacillus acidophilus and G.

Alanine racemase a promising Helicobacter pylori drug target inhibited by propanoic acid.

Eradication of Helicobacter pylori, the class 1 carcinogen, faces several obstacles, which demand alternative options to conventional drug development methods. Alanine racemase (Alr) was proposed as H. pylori drug target, inhibited by propanoic acid (PA), in a previous in silico study.

Insights into targeting SARS-CoV-2: design, synthesis, studies and antiviral evaluation of new dimethylxanthine derivatives.

Aiming to achieve efficient activity against severe acute respiratory syndrome coronavirus (SARS-CoV-2), the expansion of the structure- and ligand-based drug design approaches was adopted, which has been recently reported by our research group. Purine ring is a corner stone in the development of SARS-CoV-2 main protease (M) inhibitors. The privileged purine scaffold was elaborated to achieve additional affinity based on hybridization and fragment-based approaches.

Evaluating the ability of some natural phenolic acids to target the main protease and AAK1 in SARS COV-2.

Researchers are constantly searching for drugs to combat the coronavirus pandemic caused by SARS-CoV-2, which has lasted for over two years. Natural compounds such as phenolic acids are being tested against Mpro and AAK1, which are key players in the SARS-CoV-2 life cycle. This research work aims to study the ability of a panel of natural phenolic acids to inhibit the virus's multiplication directly through Mpro and indirectly by affecting the adaptor-associated protein kinase-1 (AAK1).

1-Benzyl-5-bromo-3-hydrazonoindolin-2-ones as Novel Anticancer Agents: Synthesis, Biological Evaluation and Molecular Modeling Insights.

Human health is experiencing several obstacles in the modern medical era, particularly cancer. As a result, the cancer therapeutic arsenal should be continually expanded with innovative small molecules that preferentially target tumour cells. In this study, we describe the development of two small molecule series (- and -) based on the 1-benzyl-5-bromoindolin-2-one scaffold that connected through a hydrazone linker to a 4-arylthiazole (-) or 4-methyl-5-(aryldiazenyl)thiazole (-) moiety.

Dual-target ligand discovery for Alzheimer's disease: triphenylphosphoranylidene derivatives as inhibitors of acetylcholinesterase and β-amyloid aggregation.

Alzheimer disease (AD) is one of the major neurodegenerative diseases that could not be prevented or completely cured and may lead to death. Here, we target AChE and β-amyloid proteins. Synthesising new triphenylphosphporanylidene derivatives based on the surveyed literature and testing their biological activity revealed promising results especially for the acetyl triphenylphosphoranylidene derivative , which showed good inhibitor activity against AChE enzyme with IC in the nanomolar range (97.

Biological Evaluation, Molecular Docking Analyses, and ADME Profiling of Certain New Quinazolinones as Anti-colorectal Agents.

Colorectal carcinogenesis is a complex process, which is linked to dysregulation of human secretory phospholipases A (hsPLA-G-IIA, hsPLA-G-, and hsPLA-G-, proteases (cathepsin-B, collagenase, thrombin, elastase, and trypsin), carbohydrate hydrolyzing enzymes (α-amylase and α-glucosidase), and free radical generating enzyme (xanthine oxidoreductase (XOR)). Therefore, some new quinazolinones were synthesized and evaluated as inhibitors against this array of enzymes as well as cytotoxic agents on LoVo and HCT-116 cells of colorectal cancer. Compounds , , , , and exhibited promising cytotoxic effects with IC values ranging from 206.

Pharmacophore based virtual screening for natural product database revealed possible inhibitors for SARS-COV-2 main protease.

The challenge continues globally triggered by the absence of an approved antiviral drug against COVID-19 virus infection necessitating global concerted efforts of scientists. Nature still provides a renewable source for drugs used to solve many health problems. The aim of this work is to provide new candidates from natural origin to overcome COVID-19 pandemic.

Novel Pyridothienopyrimidine Derivatives: Design, Synthesis and Biological Evaluation as Antimicrobial and Anticancer Agents.

The growing risk of antimicrobial resistance besides the continuous increase in the number of cancer patients represents a great threat to global health, which requires intensified efforts to discover new bioactive compounds to use as antimicrobial and anticancer agents. Thus, a new set of pyridothienopyrimidine derivatives was synthesized via cyclization reactions of 3-amino-thieno[2,3-]pyridine-2-carboxamides with different reagents. All new compounds were evaluated against five bacterial and five fungal strains.

Synthesis, Biological, and Molecular Docking Studies on 4,5,6,7-Tetrahydrobenzo[]thiophene Derivatives and Their Nanoparticles Targeting Colorectal Cancer.

Initiation of colorectal carcinogenesis may be induced by chromosomal instability caused by oxidative stress or indirectly by bacterial infections. Moreover, proliferating tumor cells are characterized by reprogrammed glucose metabolism, which is associated with upregulation of PDK1 and LDHA enzymes. In the present study, some 4,5,6,7-tetrahydrobenzo[]thiophene derivatives in addition to FeO and FeO/SiO nanoparticles (NPs) supported with a new Schiff base were synthesized for biological evaluation as PDK1 and LDHA inhibitors as well as antibacterial, antioxidant, and cytotoxic agents on LoVo and HCT-116 cells of colorectal cancer (CRC).

Repurposing of renin inhibitors as SARS-COV-2 main protease inhibitors: A computational study.

The COVID-19 pandemic has urged for the repurposing of existing drugs for rapid management and treatment. Renin inhibitors down regulation of ACE2, which is an essential receptor for SARS-CoV-2 infection that is responsible for COVID-19, in addition to their ability to act as protease inhibitors were encouraging aspects for their investigation as possible inhibitors of main protease of SARS-CoV-2 via computational studies. A Pharmacophore model was generated using the newly released SARS-COV-2 main protease inhibitors.

Roflumilast analogs with improved metabolic stability, plasma protein binding, and pharmacokinetic profile.

With the aim of studying their in vitro and in vivo pharmacokinetics, new chromatographic methods were developed for the determination of three new roflumilast synthetic analogs (I-III) as PDE-4B inhibitors in rat liver S9 fraction, phosphate buffered saline, pH 7.4, and human and rat plasma. The developed high performance liquid chromatography-ultra violet (HPLC-UV) methods were performed on a Zorbax Eclipse C8 column and UV detection was carried out at 215 nm.

Synthesis and molecular docking of new roflumilast analogues as preferential-selective potent PDE-4B inhibitors with improved pharmacokinetic profile.

In the present work, we designed and synthesized new roflumilast analogues with preferential-selective PDE-4B inhibition activity and improved pharmacokinetic properties. The unsubstituted benzo[d]thiazol-2-yl and -6-yl benzamide derivatives (4a and 6a) showed both good potency and preferential selectivity for PDE-4B. More remarkably, 6c revealed 6 times preferential PDE-4B/4D selectivity with a significant increase of in vitro cAMP and good % inhibition of TNF-α concentration.