Novel anticancer drug discovery strategies targeting hypoxia-inducible factors.

Introduction: Hypoxia is a key feature of solid tumors, associated with aggressive behaviors such as radiation and chemotherapy resistance, increased metastasis, and poor prognosis. Hypoxia-inducible factors (HIFs) are essential transcription factors that help tumor cells adapt to hypoxic environments by promoting the expression of pro-oncogenic genes. Reducing HIF activity presents a promising strategy for advancing cancer treatment.

LC-HRMS Profiling and Cytotoxic Potential of Actinomycetes Associated with the Red Sea Soft Coral Sarcophyton glaucum: In vitro and In silico Studies.

In the current study, the actinomycetes associated with the red sea-derived soft coral Sarcophyton glaucum were investigated in terms of biological and chemical diversity. Four different media, M1, ISP2, Marine Agar (MA), and Actinomycete isolation agar (AIA) were used for the isolation of three strains of actinomycetes that were identified as Streptomyces sp. UR 25, Micromonospora sp.

Assessing the Antiproliferative Potential of a Novel Combretastatin A4 Derivative Modulating Apoptosis, MAPK/ERK and PI3K/AKT Pathways in Human Breast Cancer Cells.

Background: Breast cancer is the most predominant tumor in women. Even though current medications for distinct breast cancer subtypes are available, the non-specificity of chemotherapeutics and chemoresistance imposes major obstacles in breast cancer treatment. Although combretastatin A-4 (CA-4) has been well-reported to have potential anticancer activity, studies of CA-4 reveal a decrease in its activity.

Promising Cytotoxic butenolides from the Soybean endophytic fungus Aspergillus terreus: a combined molecular docking and in-vitro studies.

Aim: This study aimed to use one strain many compounds approach (OSMAC) to investigate the cytotoxic potential of Aspergillus terreus associated with soybean versus several cancer cell lines, by means of in-silico and in vitro approaches.

Methods And Results: Fermentation of the isolated strain was done on five media. The derived extracts were investigated for their inhibitory activities against three human cancer cell lines; mammary gland breast cancer (MCF-7), colorectal adenocarcinoma (Caco-2), and hepatocellular carcinoma (HepG2) using MTT Assay.

Design and Synthesis of New Hydantoin Acetanilide Derivatives as Anti-NSCLC Targeting EGFR Mutations.

Epidermal Growth Factor Receptor (EGFR), its wild type and mutations L858R/T790M, is overexpressed in non-small cell lung cancer (NSCLC) patients and is considered an inevitable oncology target. However, while the potential EGFR inhibitors have been represented in the literature, their cellular activity failed to establish broad potency against EGFR and its mutations. This study identifies a new series of EGFR inhibitors bearing hydantoin acetanilides.

NS3 helicase inhibitory potential of the marine sponge .

In the current study, an investigation of the activity of the total extract of the marine sponge and its different fractions against the hepatitis C virus (HCV) was pursued. The results revealed that the ethyl acetate fraction exhibited the highest anti-HCV activity, with an IC value of 12.6 ± 0.

The importance of sulfur-containing motifs in drug design and discovery.

Introduction: Sulfur-containing functional groups are privileged motifs that occur in various pharmacologically effective substances and several natural products. Various functionalities are found with a sulfur atom at diverse oxidation states, as illustrated by thioether, sulfoxide, sulfone, sulfonamide, sulfamate, and sulfamide functions. They are valuable scaffolds in the field of medicinal chemistry and are part of a large array of approved drugs and clinical candidates.

In Silico and In Vitro Studies for Benzimidazole Anthelmintics Repurposing as VEGFR-2 Antagonists: Novel Mebendazole-Loaded Mixed Micelles with Enhanced Dissolution and Anticancer Activity.

Cancer is a leading cause of death worldwide and its incidence is unfortunately anticipated to rise in the next years. On the other hand, vascular endothelial growth factor receptor 2 (VEGFR-2) is highly expressed in tumor-associated endothelial cells, where it affects tumor-promoting angiogenesis. Therefore, VEGFR-2 is considered one of the most promising therapeutic targets for cancer treatment.

Coronavirus Disease (COVID-19) Control between Drug Repurposing and Vaccination: A Comprehensive Overview.

Respiratory viruses represent a major public health concern, as they are highly mutated, resulting in new strains emerging with high pathogenicity. Currently, the world is suffering from the newly evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus is the cause of coronavirus disease 2019 (COVID-19), a mild-to-severe respiratory tract infection with frequent ability to give rise to fatal pneumonia in humans.

FAK inhibitors as promising anticancer targets: present and future directions.

FAK, a nonreceptor tyrosine kinase, has been recognized as a novel target class for the development of targeted anticancer agents. Overexpression of FAK is a common occurrence in several solid tumors, in which the kinase has been implicated in promoting metastases. Consequently, designing and developing potent FAK inhibitors is becoming an attractive goal, and FAK inhibitors are being recognized as a promising tool in our armamentarium for treating diverse cancers.

Selective SIRT2 inhibitors as promising anticancer therapeutics: An update from 2016 to 2020.

Sirtuin 2 (SIRT2) is a member of the human sirtuins, which regulates various biological processes and is deemed as a novel biomarker for different cancers. Depending on the tumor type, SIRT2 knockout leads to a controversial role in tumorigenesis, however, pharmacological inhibition of SIRT2 results exclusively in growth inhibition of various cancer cells. In this respect, selective SIRT2 inhibitors hold therapeutic promise in a wide range of tumors.

In vitro inhibition and molecular docking of a new ciprofloxacin-chalcone against SARS-CoV-2 main protease.

Background/aim: SARS-CoV-2 is one of the coronavirus families that emerged at the end of 2019. It infected the respiratory system and caused a pandemic worldwide. Fluoroquinolones (FQs) have been safely used as antibacterial agents for decades.

A first-in-class anticancer dual HDAC2/FAK inhibitors bearing hydroxamates/benzamides capped by pyridinyl-1,2,4-triazoles.

Novel 5-pyridinyl-1,2,4-triazoles were designed as dual inhibitors of histone deacetylase 2 (HDAC2) and focal adhesion kinase (FAK). Compounds 5d, 6a, 7c, and 11c were determined as potential inhibitors of both HDAC2 (IC = 0.09-1.

Natural metabolites from the soft coral sp. as potential SARS-CoV-2 main protease inhibitors.

The ongoing spread of SARS-CoV-2 has created a growing need to develop effective antiviral treatments; therefore, this work was undertaken to delve into the natural metabolites of the Red Sea soft coral sp. (family Nephtheidae) as a source of potential anti-COVID-19 agents. Overall, a total of 14 structurally diverse minor constituents were isolated and identified from the petroleum ether fraction of sp.

OMA1520 and OMA1774, novel 1,2,4-triazole bearing analogs of combretastatin A-4, inhibit hepatocellular carcinoma: Histological and immunohistochemical studies.

Unlabelled: Combretastatin A-4 (CA-4) received significant interest as a potential anticancer agent in recent years. Several CA-4 analogs were synthesized and investigated to enhance the activity or solve the in vivo decreased activity of CA-4.

Aim: The present study aims to investigate the chemotherapeutic and the antiproliferative effects of the mono and the dual therapy of the newly synthesized CA-4 analogs OMA1520 and OMA1774 against hepatocellularcarcinoma (HCC) induced in male adult rats by N-methylnitrosourea (MNU).

Discovery of antiproliferative and anti-FAK inhibitory activity of 1,2,4-triazole derivatives containing acetamido carboxylic acid skeleton.

Small molecule inhibitors of the focal adhesion kinase are regarded as promising tools in our armamentarium for treating cancer. Here, we identified four 1,2,4-triazole derivatives that inhibit FAK kinase significantly and evaluated their therapeutic potential. Most tested compounds revealed potent antiproliferative activity in HepG2 and Hep3B liver cancer cells, in which 3c and 3d were the most potent (IC range; 2.

Data-set of academic difficulties among students in western Uganda during COVID-19 induced lockdown.

This academic research explicit the data-set of academic difficulties among different age groups of students studying in various schools, colleges or Universities during the COVID-19 induced lockdown. The western part of Uganda comprises 26 districts and the survey was conducted in those regions employing a simple random sampling technique. The dataset is descriptive and an aggregate of 405 students participated in this survey.

Novel Mannich bases of ciprofloxacin with improved physicochemical properties, antibacterial, anticancer activities and caspase-3 mediated apoptosis.

The design, synthesis and identification of a novel series of Mannich bases of ciprofloxacin was reported. Naphthol derivatives 2a and 2b showed highly potent cytotoxic activity among the tested compounds. Compound 2a showed broad spectrum antiproliferative activity with GI of 2.

Antimicrobial Pyridazines: Synthesis, Characterization, Cytotoxicity, Substrate Promiscuity, and Molecular Docking.

A facile and convenient synthesis of new pyridazines suitable for use as antimicrobial agents was reported. The hydrazide intermediate was coupled with various benzaldehydes and/or acetophenones and cyclized instantaneously to afford target pyridazine derivatives. The structures of new pyridazines were confirmed by IR, H- and C-NMR, elemental analysis in addition to representative LC/MS.

Potent combretastatin A-4 analogs containing 1,2,4-triazole: Synthesis, antiproliferative, anti-tubulin activity, and docking study.

A series of cis restricted 1,2,4-triazole analogs of combretastatin A-4 (CA-4) were designed and synthesized. The antiproliferative activity of these compounds was measured on hepatocellular carcinoma HepG2, leukemia HL-60, and breast cancer MCF-7 cell lines. The obtained results showed a substantial ability of the synthesized anilides to inhibit tumor growth.

Synthesis, antiproliferative, anti-tubulin activity, and docking study of new 1,2,4-triazoles as potential combretastatin analogues.

Combretastatin A4 (CA4) is a natural product characterized by a powerful inhibition of tubulin polymerization and a potential anticancer activity. However, therapeutic application of CA4 is substantially hindered due to geometric isomerization. In the current study, new cis-restricted Combretastatin A4 analogues containing 1,2,4-triazle in place of the olefinic bond were designed and synthesized.

Synthesis, cytotoxicity, docking study, and tubulin polymerization inhibitory activity of novel 1-(3,4-dimethoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazole-3-carboxanilides.

A series of novel 1-(3,4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazole-3-carboxylic acid derivatives (4a-n) were synthesized and evaluated for their in vitro cytotoxic activity against the growth of four different human cell lines (hepatocarcinoma HepG2, breast adenocarcinoma MCF-7, colon carcinoma DLD-1, and leukemia HL-60). The anilides of m-anisidine 4e, o-anisidine 4f, and 3,5-difluoroaniline 4l demonstrated best results on MCF-7 cells and mean IC50 values of 7.79, 10.