Ghassan Issa

Introduction: Ellagic acid, Formononetin, and Glycitein are bioactive polyphenols possessing anticancer activity via apoptosis, cell cycle inhibition, and oncogenic signaling pathway modulation. In particular, Ellagic acid demonstrated interesting activity towards hepatocellular carcinoma (HCC), with the potential antiangiogenic target being VEGFR1. This study explores fluorinated Ellagic acid derivatives as potential VEGFR1 inhibitors, overcoming disadvantages of Formononetin/Glycitein co-drugs, namely poor ADME properties, hERG liability, and low bioavailability. Methods: Geometry optimization was carried out using DFT with the B3LYP/6-31G(d,p) basis set. Molecular docking with AutoDock Vina was applied in order to assess binding energies and inhibitory constants. Further MD simulation was conducted under physiological conditions using the OPLS 3.0 force field. Results: Ellagic acid established stable hydrogen-bond interactions with VEGFR1. Fluorination improved predicted binding affinity, inhibitory potency, and lipophilicity. Although the co-drugs exhibited stronger binding energies, they showed less favorable predicted ADMET profiles and increased toxicity alerts. All complexes remained highly stable during MD simulations (RMSD <1 Å). Discussion: Prioritization of fluorinated Ellagic acid was conducted according to favorable MM/GBSA binding energy, inhibitory constant, lipophilicity, oral bioavailability, and lack of predicted hERG-related cardiotoxicity. Formononetin and Glycitein demonstrated lower drug-likeness and predicted oral bioavailability and had cardiotoxicity issues. Conclusion: Fluorinated Ellagic acid derivatives could be considered as potential inhibitors of VEGFR1 due to their favorable binding characteristics and structural stability, along with predicted good ADMET properties without QikProp toxicity alerts.

Introduction: Besides COX-inhibitory activities, other mechanisms underlying indomethacin's potential as an anticancer agent are being explored, including those related to the mediation of prostaglandin signaling through transmembrane receptors in solid tumors. Methods: In this mini-review, we summarize available information about modulation of transmembrane receptor signaling by indomethacin, including death receptors, EP receptors, receptor tyrosine kinases (RTKs), chemokine receptors, cannabinoid receptors, ACE2, P2X7, IP, and FZD/LRP5/6 receptors associated with Wnt pathways. Results: The presented data indicate that indomethacin may inhibit PGE₂-induced EP signaling, affect EGFR/FGFR and CXCR3 signaling pathways, increase death receptor-mediated apoptosis, and influence various types of receptor cross-talk involved in proliferation, angiogenesis, immune evasion, invasion, and metastasis. However, the most consistent results were obtained in colorectal cancer cells, while the role of indomethacin in breast, ovarian, and prostate cancers appears to be more contextual and receptor-profile dependent. Discussion: Overall, our review suggests that indomethacin functions mainly as a receptor signaling modulator rather than a selective receptor antagonist. The potential clinical application of indomethacin for cancer treatment is hindered by its poor selectivity towards COX enzymes, toxicity, and lack of specificity. Conclusion: Despite the possibility of using indomethacin as a template structure for creating more selective drugs, it seems that indomethacin cannot serve as a drug for anticancer therapy alone. This conclusion specifically positions parent indomethacin as a chemically modifiable scaffold for rational derivative development rather than as a final therapeutic endpoint.

Substantial advances have been made since the 1970s in reducing the environmental impacts of ammonia production. Renewable-driven electrochemical synthesis offers a promising pathway to decarbonize ammonia production. This review examines an integrated route in which hydrogen is generated photoelectrochemically under concentrated solar irradiation and subsequently used in electrochemical ammonia synthesis. Photoelectrochemical cells are fabricated by electrostatically depositing photosensitive particles onto cathodes to enhance light-driven hydrogen production. Hydrogen production rates and ammonia yield depend strongly on temperature and electrolyte composition. The synthesized hydrogen is fed into a molten salt electrochemical reactor that operates at atmospheric pressure and receives nitrogen from a dedicated supply. This combined solar–electrochemical approach can produce low-carbon ammonia with improved safety and reduced environmental impact, offering a scalable alternative to conventional processes.

Objective: Toys in kindergartens are frequently exposed to environmental contaminants and hand contact, making them potential reservoirs for pathogenic microorganisms. Children, with developing immune systems, are particularly vulnerable to infections. This study aimed to detect Escherichia coli, Staphylococcus aureus, and coliform bacteria on toys and to characterize toy materials using FTIR, XRD, and SEM. Methods: Swab samples were collected from toy surfaces under aseptic conditions and transported under cold-chain conditions. Samples were homogenized in buffered peptone water and serially diluted. Coliforms were detected on VRB and BGBLB media, E. coli on TBX medium, and S. aureus on Baird-Parker Agar with Egg Yolk Tellurite. Identification was confirmed via Gram staining, catalase, DNase, hemolysis, and carbohydrate fermentation tests. FTIR assessed functional groups, XRD examined crystalline structures, and SEM observed surface morphology related to microbial adhesion. Results: Bacteriological analysis showed Staphylococcus spp. (35.33%), S. aureus (5%), E. coli (1%), and coliforms (3.66%). FTIR revealed diverse polymeric structures, XRD showed varying crystallinity, and SEM indicated heterogeneous surface roughness and irregular microstructures facilitating bacterial adhesion. Conclusion: Combining microbiological analyses with FTIR, XRD, and SEM provides a comprehensive method for assessing contamination risks. Kindergarten toys can harbor potentially pathogenic microorganisms, and the structural characteristics of toy materials significantly influence microbial persistence.

Ellagic acid (EA), a naturally occurring polyphenolic compound found in fruits and medicinal plants, has gained considerable attention for its significant anticancer potential. Recent studies have shown that EA demonstrates significant anticancer effects through the modulation of various transmembrane receptor-mediated signaling pathways controlling tumor development, angiogenesis, and metastasis. This review paper summarizes the interactions of EA with the major receptors involved in the development of various cancers. The mechanisms of EA-induced anticancer effects include the inhibition of various receptors such as tyrosine kinases, vascular endothelial growth factor receptor 2 (VEGFR-2), epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), and insulin-like growth factor receptor (IGF-1R). These kinases regulate various oncogenic signaling pathways. EA inhibits the PI3K/AKT/mTOR, MAPK, and NF-κB signaling pathways, where it was shown to modulate hormone receptor signaling through estrogen receptors (ERα/ERβ) and androgen receptors. EA is also found to modulate various inflammatory receptor interactions through cytokine receptor pathways. These indications of EA with various receptors suppress the development of various cancers through the inhibition of angiogenesis, cancerous cell cycle progression, epithelial-mesenchymal transition, and metastasis, causing the apoptosis in cancerous cells. EA regulates the nuclear receptor pathway as well. These studies show that EA inhibits the development of various cancers of the gastrointestinal system, liver, pancreas, breast, prostate, lungs, bladder, and others. Overall, the interactions of EA with various receptors in the development of various cancers suggest the potential of EA as a promising anticancer agent for the prevention of cancer and can be used for in silico and in vitro studies when its structure is derivatized.

Drug development processes face significant challenges, including lengthy time requirements, high costs, and success rates below 15% in clinical trials. To optimize these costly and complex processes, the KOSTU Biochemistry Department Soykan Agar’s research group has developed an autonomous artificial intelligence called MindNexQua (MNQ). This work aims to update the drug discovery pipeline by offering an accessible, open-source, and self-sufficient alternative to expensive licensed platforms. The system has a workflow that automates the process from in silico biochemical docking to final visualization, using target receptor protein structures and drug candidate ligands as initial input. MNQ integrates RDKit for the generation of structural derivatives, AutoDock Vina for molecular docking calculations, and Mistral 7B-based large language models for interpreting results. To improve the reliability of simulations and minimize random errors, a "multi-run" strategy consisting of 20 independent simulations is applied to each ligand candidate. At the end of this process, the system automatically selects and statistically validates the "Top-5" candidate molecule with the lowest binding energy (ΔG). The findings show that the candidate molecules designed by MindNexQua exhibit high steric fit (-8.6 kcal/mol) to the active site of target proteins and display thermodynamically stable conformations. Consequently, MNQ offers a sustainable, autonomous, and integrated research ecosystem for de novo drug design and in silico molecular docking orchestration.

Objective: This comprehensive in silico computational and theoretical biochemistry/organic chemistry research study covers the inhibition methodologies of 1-BNA, which is an essential template for cancer-suppressing research. By disrupting the minor groove domain binding site of the DNA template 1-BNA dodecamer, three de novo drug candidate molecules via derivatization of anti-epileptic valproic acid (VPA) drug were designed. Methods: Calf thymus DNA (ct-DNA) sequence d(CGCGAATTCGCG)2 dodecamer (PDB ID: 1BNA) was obtained from the Protein Data Bank to study. Molecular docking simulations, the most updated docking programs of AutoDock Vina and PyRx were utilized. Molecular dynamics (MD) simulations and Absorption, distribution, metabolism and excretion (ADME) analyses were employed by Schrödinger’s Desmond software. Results: Thorough in silico results of three new derivatized analogues of VPA showed that chloro-derivatized analogue with its -9.6 kcal/mol docking score and 297.2 µM inhibition constant (IC) has a much better indication in the suppression where isopropyl and fluoro derivatized analogues possess -9.1 kcal/mol docking score with 483.8 µM IC and -8.3 kcal/mol docking score with 896.2 µM IC respectively compared to the results of pristine VPA’s -8.2 kcal/mol docking score with 863.6 µM IC. Along with the detailed ADME results, isopropyl and chloro-derivatized ligands prove their worth of being a new drug candidate. Conclusion: All results proved that the de novo derivatives of VPA illustrate better docking scores (better suppression) along with better ICs and oral absorption percentage values, meaning that the analogues possess better indications compared to pristine VPA toward the suppression of cancerous cell template DNA.

Amaç: Bu çalışmada, İstanbul ve çevresinde bulunan çeşitli market, şarküteri ve semt pazarlarından toplanan 70 adet peynir, 70 adet yufka ve 10 adet çiğ süt olmak üzere toplam 150 gıda örneği Staphylococcus aureus (S. aureus) yönünden inceledikten sonra izole edilen S. aureus suşlarının antibiyotik duyarlılıklarını araştırılması amaçlandı. Yöntem: Laboratuvara getirilen gıda örneklerinden kültürel yöntemlerini kullanarak S. aureus suşları izole edildi. S. aureus olarak tanımlanan suşların disk diffüzyon yöntemiyle her biri için 21 farklı antibiyotik diski kullanarak duyarlılıkları belirlendi. Bulgular: Çalışmada analiz edilen 150 gıda örneğinden 10 (%6,66) adedi peynirden, 7 (%4,66) adedi yufkadan ve 2 (%1,33) adedi çiğ sütten olmak üzere 19 (%12,66) S. aureus suşu izole edildi. İzole edilen 19 S. aureus suşundan 3 (%15,78) tanesi birçok antibiyotiğe (Metisilin, Penisilin, Oksasilin, Ampisilin, Ampisilin Sulbaktam) dirençli olduğunu belirlendi. Sonuç: Antibiyotik dirençli S. aureus suşları direkt temas yoluyla bulaşabileceği gibi hayvansal kökenli gıdaların tüketimi yoluyla da bulaşabilmektedir. Ülkemizde gerek tıp ve gerek veteriner hekimlik alanında antimikrobiyal direnç sorunu üzerinde entegre sörveyans sistemleri oluşturulmalı ve antimikrobiyal direnç olgusunun kontrolü için gerekli stratejiler geliştirilip uygulamaya konmalıdır.