Cairo University
  • Cairo, Giza, Egypt
Recent publications
In this study, different assortments of 2-arylquinolines and 2,6-diarylquinolines have been developed. Recently, we have developed a new series of 6,7-dimethoxy-4-alkoxy-2-arylquinolines as Topoisomerase I (TOP1) inhibitors with potent anticancer activity. Utilising the SAR outputs from this study, we tried to enhance anticancer and TOP1 inhibitory activities. Though target quinolines demonstrated potent antiproliferative effect, specifically against colorectal cancer DLD-1 and HCT-116, they showed weak TOP1 inhibition which may be attributable to their non-coplanarity. Thereafter, screening against kinase panel revealed their dual inhibitory activity against EGFR and FAK. Quinolines 6f, 6h, 6i, and 20f were the most potent EGFR inhibitors (IC50s = 25.39, 20.15, 22.36, and 24.81 nM, respectively). Meanwhile, quinolines 6f, 6h, 6i, 16d, and 20f exerted the best FAK inhibition (IC50s = 22.68, 14.25, 18.36, 17.36, and 15.36 nM, respectively). Finally, molecular modelling was employed to justify the promising EGFR/FAK inhibition. The study outcomes afforded the first reported quinolines with potent EGFR/FAK dual inhibition.
On account of its crucial role in the virus life cycle, SARS-COV-2 NSP13 helicase enzyme was exploited as a promising target to identify a novel potential inhibitor using multi-stage structure-based drug discovery approaches. Firstly, a 3D pharmacophore was generated based on the collected data from a protein-ligand interaction fingerprint (PLIF) study using key interactions between co-crystallised fragments and the NSP13 helicase active site. The ZINC database was screened through the generated 3D-pharmacophore retrieving 13 potential hits. All the retrieved hits exceeded the benchmark score of the co-crystallised fragments at the molecular docking step and the best five-hit compounds were selected for further analysis. Finally, a combination between molecular dynamics simulations and MM-PBSA based binding free energy calculations was conducted on the best hit (compound FWM-1) bound to NSP13 helicase enzyme, which identified FWM-1 as a potential potent NSP13 helicase inhibitor with binding free energy equals −328.6 ± 9.2 kcal/mol.
A series of novel 1,2,3-triazole-linked ciprofloxacin-chalcones 4a-j were synthesised as potential anticancer agents. Hybrids 4a-j exhibited remarkable anti-proliferative activity against colon cancer cells. Compounds 4a-j displayed IC50s ranged from 2.53-8.67 µM, 8.67–62.47 µM, and 4.19–24.37 µM for HCT116, HT29, and Caco-2 cells; respectively, whereas the doxorubicin, showed IC50 values of 1.22, 0.88, and 4.15 µM. Compounds 4a, 4b, 4e, 4i, and 4j were the most potent against HCT116 with IC50 values of 3.57, 4.81, 4.32, 4.87, and 2.53 µM, respectively, compared to doxorubicin (IC50 = 1.22 µM). Also, hybrids 4a, 4b, 4e, 4i, and 4j exhibited remarkable inhibitory activities against topoisomerase I, II, and tubulin polymerisation. They increased the protein expression level of γH2AX, indicating DNA damage, and arrested HCT116 in G2/M phase, possibly through the ATR/CHK1/Cdc25C pathway. Thus, the novel ciprofloxacin hybrids could be exploited as potential leads for further investigation as novel anticancer medicines to fight colorectal carcinoma.
Purpose: To evaluate the overall survival (OS), local progression-free survival (PFS) and prognostic factors of patients with colorectal cancer liver metastases (CRLM) undergoing microwave ablation (MWA). Method: A total of 132 patients were retrospectively enrolled who had been treated between 2010 and 2018. For the evaluation of survival rates, all patients were divided according to their indications (curative n = 57 and debulking (patients with additional non-target extrahepatic metastases) n = 75). In total, 257 ablations were evaluated for prognostic factors: number of liver metastases, primary tumor origin (PTO), diameter and volume of metastases, duration and energy of ablation. Results: The OS was 32.1 months with 93.2% of patients free from recurrence at 28.3 months (median follow-up time). The one- year and three-year OS were 82.72% and 41.66%, respectively. The OS and recurrence-free survival of the curative group were statistically significantly higher than the debulking group (p < .001). Statistically significant prognostic factors for OS included the location of the primary tumor (p < .038) and the number of metastases (all p < .017). Metastasis diameter and volume and ablation duration and energy had no significant correlation with survival (p > .05). Conclusions: Satisfactory OS and local tumor PFS can be achieved in patients with CRLM using MWA with the number of metastases and the location of the primary tumor influencing the outcome of patients. The metastasis's size and the duration and energy used for ablation were not of significant prognostic value.
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22,164 members
Shymaa S. Medany
  • Department of Chemistry
Mohamed hassan Fahmy
  • Faculty of Medicine
Tamer Macky
  • Department of Ophthalmology
Information
Address
El-Gammaa, 12613, Cairo, Giza, Egypt
Head of institution
Mohamed Osman El-Khosht
Website
www.cu.edu.eg