One of the multifactorial worldwide health syndromes is diabetes mellitus which is increasing at a disturbing rate. The inhibition of α-glucosidase, an enzyme that catalyzes starch hydrolysis in the intestine, is one helpful therapeutic approach for controlling hyperglycemia related to type-2 diabetes. To discover α-glucosidase inhibitors, some 2-hydrazolyl-4-thiazolidinone hybrids (3a-e) were synthesized from new one-pot reaction procedures. Next, their chemical structures were confirmed by 1H NMR, 13C NMR, and FT-IR spectra, and elemental analysis technique. Then, the α-glucosidase inhibitory activity of the titled compounds was evaluated. Among them, derivatives 3b and 3c revealed the highest activity against α-glucosidase compared to acarbose as a drug. Enzyme kinetic studies of the most active derivative (3b) indicated a competitive inhibition. Finally, molecular modeling studies were accomplished to describe vital interactions of the most potent compounds (3b and 3c) with the α-glucosidase enzyme.

Herbs have been used as medicines since antiquity, and it has been discovered that the human body responds well to herbal remedies. Research on the effect of butin was conducted in the current study in the alloxan-induced diabetic rat paradigm. A total of 30 Wistar rats were randomly assigned into the following groups (n = 6): I-Normal; II-Alloxan-induced (50 mg/kg); III-Alloxan + butin 25 mg/kg; IV-Alloxan + butin 50 mg/kg; V-Butin per se 50 mg/kg. Various diabetic parameters (blood glucose, insulin, HbA1c), lipid profile, inflammatory (TNF-α, IL-1β, IL-6 and NF-κB), antioxidant enzymes (CAT, SOD and GSH), oxidative stress indicators (MDA), apoptosis marker (caspase-3), hepatic markers (ALT and AST), and histopathological changes were assessed. Additionally, molecular docking and dynamics were performed to evaluate the interaction of butin with target proteins. Butin treatment, at both doses, significantly restored biochemical parameters and preserved pancreatic histopathology in diabetic rats. It effectively modulated blood parameters, lipid profiles, inflammatory markers, apoptosis, antioxidant enzyme activity, oxidative stress, and hepatic markers. Molecular docking revealed that butin binds to proteins such as caspase-3 (1NME), NF-κB (1SVC), and serum insulin (4IBM) with binding affinities of - 7.4, - 6.5, and - 8.2 kcal/mol, respectively. Molecular dynamics simulations further suggested that butin induces significant conformational changes in these proteins. Butin exhibits potential effects against alloxan-induced diabetic rats by restoring biochemical balance, reducing inflammation, and protecting pancreatic tissue. Its binding to key proteins involved in apoptosis and inflammation highlights its therapeutic potential in diabetes management.

Aim: Twenty compounds of 6-nitro-4-substituted quinazolines were synthesized.Materials & methods: 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.Results & discussion: compound 6c showed a superior to nearly equal cytotoxicity in comparison to gefitinib, it also revealed a good safety profile. Compound 6c caused a cell cycle arrest at G2/M phase in addition to induction of apoptosis. A molecular docking study was conducted on the most active compounds to gain insights of their binding mode in the active site of EGFR enzyme besides ADME prediction of their physicochemical properties and drug likeness profile.
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In the quest to combat tuberculosis, DprE1, a challenging target for novel anti-tubercular agents due to its small size and membrane location, has been a focus of research. DprE1 catalyzes the transformation of DPR into Ketoribose DPX, with Benzothiazinone emerging as a potent pharmacophore for inhibiting DprE1. Clinical trial drugs such as BTZ043, BTZ038, PBTZ169, and TMC-207 have shown promising results as DprE1 inhibitors. This study employed pharmacophore mapping of Pyrazolopyridine, Dinitrobenzamide, and Benzothiazinone derivatives to identify crucial features for eliciting a biological response. Benzothiazinone (Ligand code: 73) emerged as a reference ligand with a fitness score of 3.000. ROC analysis validated the pharmacophore with an excellent score of 0.71. To build a 3D QSAR model, a series of Benzothiazinone congeneric derivatives were explored. The model exhibited strong performance, with a standard deviation of 0.1531, a correlation coefficient for the training set (R2) value of 0.9754, and a correlation coefficient for test set Q2 value of 0.7632, indicating robust predictive capabilities. Contour maps guided the design of novel benzothiazinone derivatives, emphasizing steric, electrostatic, hydrophobic, H-bond acceptor, and H-bond donor groups for structure-activity relationships. Docking studies against PDB ID: 4NCR demonstrated favorable scores, with interactions aligning well with the in-built ligand 26 J. Docking validation via RMSD values supported the reliability of the docking results. This comprehensive approach aids in the design of novel benzothiazinone derivatives with potential anti-tubercular properties, contributing to the development of novel anti-tubercular agents which can be pivotal in the eradication of tuberculosis.

BACKGROUND: The threshold of a Leg Length Discrepancy (LLD) by clinical examination on a sheet or centimeter paper (CP) is not known precisely whether or not it concerns limbs equipped with a hip prosthesis. We therefore conducted a prospective in silico study in order to: (1) determine the reproducibility and sensitivity of the clinical measurement of the LLD in different ideal and \"degraded\" clinical situations, (2) determine the threshold from which the human eye is capable of detecting a length inequality in clinic, (3) to determine whether the use of a graduated support (centimeter paper) improves the clinical measurement threshold.
OBJECTIVE: Our hypothesis was that clinical measurement on a centimeter support would improve clinical measurement accuracy.
METHODS: This was an in silico study, the experiment was conducted on a mannequin. Different inequalities were created on a mannequin and photographed with a total of 30 inequalities from -22 to +22 mm on sheet or centimeter paper (CP). This was a multicenter study, with 40 different readers. We asked the readers to make a second measurement one month later. We evaluated the inter- and intra-observer reproducibility. The error rate at the threshold of 3 mm and 5 mm were calculated versus the gold standard. Finally, we determined at which thresholds respectively 75% and 95% of the measurements were correct.
RESULTS: A total of 4140 measurements were performed and compared to the gold standard. With a threshold of 75% accurate measurement, the LLD detection threshold was 2.8 mm on centimeter paper and 4.5 mm on sheet. With a threshold of 95% accurate measurement, the LLD detection threshold was 3.4 mm on centimeter paper and 5.2 mm on sheet. Interobserver agreement (assessed overall on the 40 observers by Krippendorff\'s generalized Kappa) was 0.86 (95% confidence interval (CI95%) = 0.79 to 0.92) on CP and 0.71 (CI95% = 0.63 to 0.79) on sheet. Intra-observer agreement assessed by the intraclass correlation coefficient among observers who made 2 measurements had a median value (IQR) of 0.96 (0.94 to 0.99) on CP and 0.90 (0.83 to 0.94) on sheet.
CONCLUSIONS: The clinical detection threshold on sheet at the patient\'s bed appears close to 5 mm. A more precise measurement is possible with graduated centimeter paper. A study in daily practice on patients in real situations would confirm our results.
METHODS: III; prospective diagnostic comparative in Silico study.

The emergence of bacterial resistance to antimicrobial agents poses a serious threat to the effectiveness of treating bacterial illnesses. A major factor contributing to antimicrobial resistance is biofilm formation, driven by quorum sensing (QS). QS suppression inhibits the QS signaling pathway, obstructing cell-to-cell communication. This study focuses on N-(pyrimidin-2-yl)alkyl/arylamide derivatives, which were designed, synthesized, and characterized for their QS inhibitory effects. Among the synthesized compounds (3a-j), compounds 3b, 3d, and 3h exhibited the highest QS inhibitory activity, with inhibition zones of 17.66 ± 6.17, 14.00 ± 6.24, and 17.33 ± 0.66 mm, respectively. Further, molecular docking studies revealed binding affinities between - 8.4 and - 6.3 kcal/mol, indicating strong interactions with the target proteins. Moreover, molecular dynamic simulations confirmed the stability of the protein-ligand complexes for compounds 3b and 3 h. Additionally, in-silico methods were employed to predict the physicochemical properties of these molecules. Overall, these findings underscore the potential of N-(pyrimidin-2-yl)alkyl/arylamide derivatives as QS inhibitors, offering a new perspective for developing alternative antimicrobial therapies.

In this paper, we present the synthesis and characterization of two known sulfonyl hydrazides (1 and 2) and their new sulfonyl hydrazone derivatives (9-20), as well as in vitro and in silico investigations of their cytotoxic properties against human lung (A549) and human breast (MCF-7) cancer cell lines. The target compounds (9-20) obtained in high yields were synthesized for the first time by a multi-step reaction, and their structures were confirmed by elemental analysis and various spectral techniques, including FT-IR, 1H-, and 13C-NMR. The antiproliferative profiles of these compounds (1, 2, and 9-20) in this study were determined at concentrations of 200, 100, 50, and 25 µM against selected cancer cell lines for 72 h using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. Except for compounds 1 and 2, other compounds (9-20) demonstrated cytotoxic activity at concentrations lower than 200 µM. The newly synthesized compounds (9-20) demonstrated antiproliferative activities at a micromolar level, with IC50 values in the range of 29.59-176.70 μM for the A549 cell line and 27.70-170.30 μM for the MCF-7 cell line. Among these compounds, compound 15 (IC50 = 29.59 μM against A549 cell line and IC50 = 27.70 μM against MCF-7 cell line) showed the highest cytotoxic activity against these two cancer cell lines compared to the reference drug cisplatin (IC50 = 22.42 μM against A549 cell line and IC50 = 18.01 μM against MCF-7 cell line). From docking simulations, to establish a plausible binding mode of compounds, we noticed that compound 15 demonstrated the highest affinity (-6.8508 kcal/mol) for estrogen receptor-beta (ERbeta) compared to others, suggesting promising ERbeta binding potential. Most compounds followed Lipinski\'s rule of five, with acceptable logP values. Additionally, all had mixed gastrointestinal absorption and limited blood-brain barrier permeability. Overall, our study proposed new sulfonyl hydrazones as a potential class of anticancer agents.

This study is the first to investigate the chemical composition and antioxidant, anti-inflammatory, and cytotoxic activities of Peperomia leptostachya leaf oil. A yellow oil was obtained through hydro-distillation, with a yield of 0.1% (w/w). The GC-MS analysis revealed 66 compounds, constituting 99.6% of the oil. Sesquiterpene hydrocarbons predominated (70.4%), followed by monoterpene hydrocarbons (13.2%), oxygenated sesquiterpenes (12.4%), non-terpenic compounds (2.0%), and oxygenated monoterpenes (1.6%). Major constituents included germacrene D (25.1%), (E)-caryophyllene (17.4%), bicyclogermacrene (6.6%), α-pinene (6.2%), and β-pinene (4.7%). The assessment of antioxidant capacity via 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay yielded a weak effect, with an IC50 value > 100 µg/mL. The inhibition of lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells was quantified using the MTT assay, showing an IC50 value of 15.15 ± 0.68 µg/mL. Furthermore, cytotoxic effects on SK-LU-1 cell line growth were evaluated using the sulforhodamine B assay, resulting in an IC50 value of 37.45 ± 2.43 μg/mL. The anti-inflammatory activity was notable among the analyzed bioactivities of this oil. By employing a computational model, the predominant secondary metabolites in the essential oil were selected as candidates for interaction analysis with cyclooxygenase-2, an enzyme implicated in the inflammatory response. Our findings suggest that P. leptostachya leaf oil could serve as a potential source of natural compounds with prospective therapeutic effects in treating inflammatory conditions.

Aim: Our investigation aims to estimate the antifungal effect of propranolol hydrochloride (PNL). Methods: Oleosomes (OLs) were fabricated by thin-film hydration and evaluated for entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and amount of drug released after 6 h Q6h (%). Results: The optimal OL showed a rounded shape with optimum characteristics. The ex-vivo permeation and confocal laser scanning microscopy verified the prolonged release and well deposition of PNL-loaded OLs-gel. The in-silico assessment demonstrated the good stability of PNL with OLs\' ingredients. In vivo evaluations for PNL-loaded OLs-gel showed a good antifungal impact against Candida albicans with good safety. Conclusion: This work highlights the potential of PNL-loaded OLs-gel as a potential treatment for candida vaginal infection.
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The World Health Organization has considered the infertility as an international public health problem. Infertility affect nearly 1 in 7 couples and male component contributes to 50% of infertility cases. There is a clear link between male infertility and some cancers such as testicular germ cell, prostate and colon cancers. Two possibilities support this finding: 1) Cancer treatments can affect the fertility factors 2) Genetic profile of infertility genes have been altered in cancer patients. Although the previously published researches have mostly focused on the first factor, no article has yet confirmed the role of genetic factors. In this in silico study, we collected the large number of genes (n = 17703) involved in infertility. These genes were collected from NGS panel tests of male infertility and comprehensive literature review or online data base. The Prostate Adenocarcinoma genomic and transcriptomics raw data were downloaded from the cBioPortal Cancer dataset. This included with 494 patients of Prostate Cancer with 494 mutation data, 489 with CNA and 493 with RNA seqV2 data. TCGA RNA-Seq raw data was extracted in R using the cgdsr extension package with a threshold of ±2 relative to normal samples. The observed data showed that male infertility genes have been distributed through the human genome. Among the 17703 analyzed genes of this study, the genomic profile of three genes including OR9Q1, H4C6 and PSG7 were changed approximately in 100% of (n = 493) patients. In most of patients (>98%), genetic alteration was related to change in gene expression. In conclusion, this study showed that the genomic and transcriptomics patterns of some male-infertility genes are notably altered in patients of prostate cancer and suggested a possible role of genetic factors in occurrence of infertility in cancer patients. Our information can be used as a source for the design of genetic database of male-infertility.