The aim of the study was to conduct phytochemical and pharmacological investigations of Wrightia coccinea (Roxb. ex Hornem.) Sims via several in vitro, in vivo, and in silico models. A total of four compounds were identified and isolated from the methanol extract of the bark and the methanol extract of the seed pulp of W. coccinea through successive chromatographic techniques and were characterized as 3β-acetyloxy-olean-12-en-28-ol (1), wrightiadione (2), 22β-hydroxylupeol (3), and β-sitosterol (4) by spectroscopic analysis. The aqueous fraction of the bark and chloroform fraction of the fruits provided the most potent antioxidant capacity (IC50 = 7.22 and 4.5 µg/mL, respectively) in DPPH free radical scavenging assay compared with the standard ascorbic acid (IC50 = 17.45 µg/mL). The methanol bark extract and the methanol fruit coat extract exerted anti-diarrheal activity by inhibiting 74.55 ± 0.67% and 77.78 ± 1.5% (mean ± SEM) of the diarrheal episode in mice, respectively, after four hours of loading the samples. In the hypoglycemic test, the methanol bark extract and the methanol fruit coat extract (400 mg/kg) produced a significant (p < 0.05) reduction in the blood glucose level in mice. Both doses of the plant extracts (200 mg/kg and 400 mg/kg) used in the study induced a significant (p < 0.05) increase in pain reaction time. The in vitro and in vivo findings were supported by the computational studies. The isolated compounds exhibited higher binding affinity compared with the standard drugs towards the active binding sites of glutathione reductase, epidermal growth factor receptor (EGFR), kappa opioid receptor, glucose transporter 3 (GLUT 3), Mu opioid receptor, and cyclooxygenase 2 (COX-2) proteins due to their potent antioxidant, cytotoxic, anti-diarrheal, hypoglycemic, and central and peripheral analgesic properties, respectively. The current findings concluded that W. coccinea might be a potential natural source for managing oxidative stress, diarrhea, hyperglycemia, and pain. Further studies are warranted for extensively phytochemical screening and establishing exact mechanisms of action.

The combretastatins (cis-stilbenoid molecules) have received significant interest because of their simple chemical structures, excellent antiproliferative activity, and novel anti-tubulin molecular mechanism of action. Significant efforts have been carried out aiming at stabilizing the active cis-isomers. A new series of cis-vinylamide derivatives containing trimethoxyphenyl moiety were synthesized and characterized. Their anticancer activities were evaluated in vitro against MCF-7 breast cancer cell line. Compounds 2f, 3, and 5 displayed potent cytotoxic activity against the breast cancer cell line compared with CA-4 as the reference compound. The microtubule polymerization assay and flow cytometry analysis confirmed that the cytotoxic activity of compound 3 was related to inhibitory activity against tubulin polymerization. Compound 3 showed pro-apoptotic activity by inducting a significant increase in the percentage of pre-G1 phase in DNA flow cytometry compared to untreated control. The pro-apoptotic activity of compound 3 was inferred by a significant increase in the percentage of fluorescent annexin V/PI positive apoptotic cells. It also increased the level of caspase 3 compared to the untreated control.

Epithelial cell transforming 2 (ECT2) is a potential oncogene and a number of recent studies have correlated it with the progression of several human cancers. Despite this elevated attention for ECT2 in oncology-related reports, there is no collective study to combine and integrate the expression and oncogenic behavior of ECT2 in a panel of human cancers. The current study started with a differential expression analysis of ECT2 in cancerous versus normal tissue. Following that, the study asked for the correlation between ECT2 upregulation and tumor stage, grade, and metastasis, along with its effect on patient survival. Moreover, the methylation and phosphorylation status of ECT2 in tumor versus normal tissue was assessed, in addition to the investigation of the ECT2 effect on the immune cell infiltration in the tumor microenvironment. The current study revealed that ECT2 was upregulated as mRNA and protein levels in a list of human tumors, a feature that allowed for the increased filtration of myeloid-derived suppressor cells (MDSC) and decreased the level of natural killer T (NKT) cells, which ultimately led to a poor prognosis survival. Lastly, we screened for several drugs that could inhibit ECT2 and act as antitumor agents. Collectively, this study nominated ECT2 as a prognostic and immunological biomarker, with reported inhibitors that represent potential antitumor drugs.

Triazole-based thiosemicarbazone derivatives (6a–u) were synthesized then characterized by spectroscopic techniques, such as 1HNMR and 13CNMR and HRMS (ESI). Newly synthesized derivatives were screened in vitro for inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All derivatives (except 6c and 6d, which were found to be completely inactive) demonstrated moderate to good inhibitory effects ranging from 0.10 ± 0.050 to 12.20 ± 0.30 µM (for AChE) and 0.20 ± 0.10 to 14.10 ± 0.40 µM (for BuChE). The analogue 6i (IC50 = 0.10 ± 0.050 for AChE and IC50 = 0.20 ± 0.050 µM for BuChE), which had di-substitutions (2-nitro, 3-hydroxy groups) at ring B and tri-substitutions (2-nitro, 4,5-dichloro groups) at ring C, and analogue 6b (IC50 = 0.20 ± 0.10 µM for AChE and IC50 = 0.30 ± 0.10 µM for BuChE), which had di-Cl at 4,5, -NO2 groups at 2-position of phenyl ring B and hydroxy group at ortho-position of phenyl ring C, emerged as the most potent inhibitors of both targeted enzymes (AChE and BuChE) among the current series. A structure–activity relationship (SAR) was developed based on nature, position, number, electron donating/withdrawing effects of substitution/s on phenyl rings. Molecular docking studies were used to describe binding interactions of the most active inhibitors with active sites of AChE and BuChE.

Background: Early detection and screening of breast cancer (BC) might help improve the prognosis of BC patients. This study evaluated the use of serum microRNAs (miRs) as non-invasive biomarkers in BC patients. Methods: Using quantitative real-time polymerase chain reaction, we evaluated the serum expression of four candidate miRs (miR-155, miR-373, miR-10b, and miR-34a) in 99 Egyptian BC patients and 40 healthy subjects (as a control). The miRs expression was correlated with clinicopathological data. In addition, the sensitivity and specificity of the miRs were determined using receiver operating characteristic (ROC) curve analysis. Results: Serum miR-155, miR-373, and miR-10b expression were significantly upregulated (p < 0.001), while serum miR-34a was downregulated (p < 0.00) in nonmetastatic (M0) BC patients compared to the control group. In addition, serum miR-155 and miR-10b were upregulated in BC patients with large tumor sizes and extensive nodal involvement (p < 0.001). ROC curve analysis showed high diagnostic accuracy (area under the curve = 1.0) when the four miRs were combined. Serum miR-373 was significantly upregulated in the human epidermal growth factor 2–negative (p < 0.001), estrogen receptor–positive (p < 0.005), and progesterone receptor (PR)-positive (p < 0.024) in BC patients, and serum miR-155 was significantly upregulated in PR-negative (p < 0.001) BC patients while both serum miR-155 and miR-373 were positively correlated with the tumor grade. Conclusions: Circulating serum miR-155, miR-373, miR-10b, and miR-34a are potential biomarkers for early BC detection in Egyptian patients and their combination shows high sensitivity and specificity.