15001-44-2Relevant academic research and scientific papers
A facile synthesis, drug-likeness, and in silico molecular docking of certain new azidosulfonamide–chalcones and their in vitro antimicrobial activity
Mostafa, Yaser A.,Mustafa, Muhamad
, (2020)
Abstract: New azidosulfonamide–chalcone derivatives were designed and synthesized. Their structures were elucidated by 1H and 13C NMR spectral analyses, in addition to elemental analyses. The synthesized derivatives were tested for their antimicrobial activity against a wide variety of Gram-positive, Gram-negative, and fungal strains. Three azidosulfonamide–chalcones showed relatively broad activity against tested strains. Two compounds exhibited eminent antibacterial activity toward S. aureus, M. luteus, and S. marcens (better than ampicillin trihydrate). The synthesized compounds exhibited moderate activity against K. pneumonia and a lower ability to inhibit E. coli growth. Among six tested fungal species, the most potent derivatives demonstrated strong activity toward only two of the fungal strains (T. rubrum and G. candidum). Assessment of drug-likeness, bioavailability, and promiscuity indicated that the compounds are viable drug candidates. In silico molecular docking analysis revealed that the synthesized azidosulfonamide–chalcones successfully occupied pterin-binding site of the dihydropteroate synthase (DHPS), implying that the prepared compounds could exert their activity by the inhibition of the microbial DHPS enzyme. These results provided essential information for the prospective design of more effective antimicrobial compounds. Graphic abstract: [Figure not available: see fulltext.]
Development of new hetero-steroid hybrids with antiproliferative activity against MCF-7 breast cancer cells
Mustafa, Muhamad,El-Kardocy, Ahmed,Mostafa, Yaser A
, p. 137 - 149 (2021)
Abstract: In continuation of our efforts to develop new antiproliferative agents that could be effective and selective in treatment of cancer, we designed and synthesized new hybrid structures containing an arylsulfonamide scaffold linked to a steroidal skeleton through a 1,2,3-triazole ring. Both in vitro cytotoxicity on breast MCF-7 cancer cells and human placental aromatase enzyme (pAROM) inhibition assays were performed on new hybrids. All new hybrids showed marked cytotoxic activity against breast MCF-7 cancer cells (IC50 = 3.56–43.76?μM) in comparison to staurosporine (IC50 = 4.06?μM). Tumor selectivity index was higher for some of the new hybrids on normal fibroblast (F-180) cells (TS = 1.5–25) in comparison to staurosporine (TS = 2.5). The p-nitro derivative exhibited the best inhibitory activity on the pAROM with an IC50 of 64.6?ng/cm3, compared to hybrids unsubstituted derivative, p-bromo derivative, and letrozole (IC50 = 375.14, 269.86, and 132.86?ng/cm3, respectively). Furthermore, the p-nitro hybrid arrested the cell cycle selectively at the G2/M phase, in addition to inducing both early and late apoptotic processes of breast MCF-7 cancer cells. Molecular docking studies were performed within pAROM to explore the binding modes of the new hybrids. Collectively, the antiproliferative profile of new hybrids indicates how good they are as promising leads for developing tumor-specific cytotoxins, and deserve further studies to optimize their structure and in vivo activity. Graphic abstract: [Figure not available: see fulltext.]
Aryl azide-sulfonamide hybrids induce cellular apoptosis: synthesis and preliminary screening of their cytotoxicity in human HCT116 and A549 cancer cell lines
El-Kardocy, Ahmed,Mustafa, Muhamad,Ahmed, Esam R.,Mohamady, Samy,Mostafa, Yaser A.
, p. 2088 - 2098 (2019)
Simple, small, drug-like molecules bearing aryl azide and aryl sulfonamide moieties were designed and synthesized. The cytotoxic activity of these compounds was measured on colon cancer HCT116, lung cancer A549, and normal fibroblast cells F180 cell lines. All the synthesized compounds showed a significant cytotoxic activity below 100 μM in both HCT116 and A549 cells. Compounds 10e and 10f exhibited the most potent activity with IC50 values of 2.20 and 6.27 μM on A549 and HCT116 cells, respectively. Also, compounds 10e and 10f showed significant tumor selectivity on HCT116 and A549 cell lines when compared with the reference cytotoxic agent staurosporine. This indicated the promising safety of these compounds on normal cells. In addition, flow cytometry studies showed that HCT116 cell lines treated with the most active compound 10f were arrested in the G2/M phase of the cell cycle. 10f boosted both early and late apoptosis at HCT116 cells. A hypothetical pharmacophore model was built using 14 reported potent carbonic anhydrase I inhibitors. The pharmacophoric study revealed that the tested sulfonamide derivatives 10e and 10f showed significant fitting on the pharmacophore query with reasonable RMSD values. Molecular docking study showed a chelation reaction with the key Zn atom, in addition to different hydrogen bonding, and van der Waals interactions with several important amino acids inside the CA Ι active site. [Figure not available: see fulltext.].
