Browsing by Author "Nissan, Yassin M"

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Dapson in heterocyclic chemistry, part VIII: synthesis, molecular docking and anticancer activity of some novel sulfonylbiscompounds carrying biologically active 1,3-dihydropyridine, chromene and chromenopyridine moieties
(Springer Link, 2012-07) Al-Said, Mansour S; Ghorab, Mostafa M; Nissan, Yassin M
[HTML] من springer.com Dapson in heterocyclic chemistry, part VIII: synthesis, molecular docking and anticancer activity of some novel sulfonylbiscompounds carrying biologically active 1, 3 … المؤلفون Mansour S Al-Said, Mostafa M Ghorab, Yassin M Nissan تاريخ النشر 2012/12/1 مجلة Chemistry Central Journal المجلد 6 الإصدار 1 الصفحات 64 الناشر Springer International Publishing الوصف Several new sulfonebiscompounds having a biologically active 1,2-dihydropyridine-2-one 3–19, acrylamide 20, chromene 21, 22 and chromenopyridine 23, 24 moieties were synthesized and evaluated as potential anticancer agents. The structures of the products were confirmed via elemental analyses and spectral data. The screening tests showed that many of the biscompounds obtained exhibited good anticancer activity against human breast cell line (MCF7) comparable to doxorubicin which was used as reference drug. Compounds 11, 17 and 24 showed IC50 values 35.40 μM, 29.86 μM and 30.99 μM, respectively. In order to elucidate the mechanism of action of the synthesized compounds as anticancer agents, docking on the active site of farnesyltransferase and arginine methyltransferase was also performed and good results were obtained.
Design, synthesis, and biological evaluation with molecular dynamics study of novel pyrazolo[3,4-d] pyrimidine derivatives as anti-cancer agents
(Royal Society of Chemistry, 2023-06) Shaban, Rania M; Samir, Nermin; Nissan, Yassin M; Abouzid, Khaled A. M
In continuation of our efforts to discover new structural chemotypes with significant chemotherapeutic activities, a novel series of pyrazolo[3,4-d]pyrimidine-based compounds linked to a piperazine ring, bearing different aromatic moieties, through different linkages was designed and synthesized as FLT3 inhibitors. All of the newly synthesized compounds were evaluated for their cytotoxicity on 60-NCI cell lines. Compounds with the piperazine acetamide linkage XIIa–f & XVI exhibited a remarkable anticancer activity among all of the tested compounds, especially against non-small cell lung cancer, melanoma, leukemia and renal cancer models. Furthermore, compound XVI (NSC no – 833644) was further screened with a 5-dose assay on nine subpanels and exhibited a GI50 between 1.17 and 18.40 mM. On the other hand, molecular docking and dynamics studies were performed to predict the binding mode of the newly synthesized compounds in the FLT3 binding domain. Finally, through a predictive kinetic study, several ADME descriptors were calculated.
New proapoptotic chemotherapeutic agents based on the quinolone‑3‑carboxamide scafold acting byVEGFR‑2 inhibition
(Springer, 2023-06) El‑Fakharany, Zeinab S; Nissan, Yassin M; Sedky, Nada K; Arafa, Reem K.; Abou‑Seri, Sahar M.
In the current study, we designed and synthesized a series of new quinoline derivatives 10a-p as antiproliferative agents targeting cancer through inhibition of VEGFR-2. Preliminary molecular docking to assess the interactions of the designed derivatives with the binding site of VEGFR-2 (PDB code: 4ASD) displayed binding poses and interactions comparable to sorafenib. The synthesized compounds exhibited VEGFR-2 inhibitory activity with IC50 ranging from 36 nM to 2.23 μM compared to sorafenib (IC50 = 45 nM), where derivative 10i was the most potent. Additionally, the synthesized derivatives were evaluated in vitro for their cytotoxic activity against HepG2 cancer cell line. Seven compounds 10a, 10c, 10d, 10e, 10i, 10n and 10o (IC50 = 4.60, 4.14, 1.07, 0.88, 1.60, 2.88 and 2.76 μM respectively) displayed better antiproliferative activity than sorafenib (IC50 = 8.38 μM). Compound 10i was tested against Transformed Human Liver Epithelial-2 normal cell line (THLE-2) to evaluate its selective cytotoxicity. Furthermore, 10i, as a potent representative of the series, was assayed for its apoptotic activity and cell cycle kinetics’ infuence on HepG2, its efects on the gene expression of VEGFR-2, and protein expression of the apoptotic markers Caspase-7 and Bax. Compound 10i proved to have a potential role in apoptosis by causing signifcant increase in the early and late apoptotic quartiles, a remarkable activity in elevating the relative protein expression of Bax and Caspase-7 and a signifcant reduction of VEGFR-2 gene expression. Collectively, the obtained results indicate that compound 10i has a promising potential as a lead compound for the development of new anticancer agents
Non-ulcerogenic pyrazolyl 2-hydroxychalcones and pyrazolylpyrazolines derived from naturally existing furochromone (khellin): semi-synthesis, docking study and anti-inflammatory activit
(national library of medicine, 2021-04) Ragab, Fatma Abd El-Fattah; Nissan, Yassin M; Salem, Mohammad Alaraby; Ali, Mamdouh Moawad; Mohamed, Ahmed Abbass
Novel pyrazolyl 2-hydroxychalcone derivatives 3a-e and pyrazolylpyrazoline derivatives 4a-e and 5a-j derived from the naturally existing furochromone (Khellin) were synthesized and evaluated for their in vivo anti-inflammatory activity. Most of the synthesized compounds showed better or comparable activity to that of Diclofenac as reference drug. Twelve compounds were evaluated for their ulcerogenic potential and exhibited no ulcerogenic effect. In addition compounds 3c, 5c and 5h as examples showed PGE2 inhibition % 88.86, 65.87 and 44.06, respectively and TNFα inhibition % 48.62, 31.11 and 16.02, respectively in rat serum samples. Compounds 3c, 5c, 5h and Celecoxib were subjected to in vitro COX-1 and COX-2 inhibition assay, showed selectivity index 45.04, 102.04, 131.58 and 185.18, respectively. The computational finding supported those of in vitro, where the pyrazolylpyrazolines interacted with the COX-2 enzyme in a similar orientation to that of Celecoxib, while chlacones were found to exhibit similar orientation to that of Diclofenac.
Novel coumarin-pyrazoline hybrids: synthesis, cytotoxicity evaluation and molecular dynamics study
(ROYAL SOC CHEMISTRY, THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND, 2021-09) Ragab, Fatma A; Eissa, Amal A. M; Fahim, Samar H; Salem, Mohammad Alaraby; Gamal, Mona A; Nissan, Yassin M
A novel series of coumarin-pyrazoline hybrids 3a-f, 4a-c and 5a-c have been synthesized and tested for their antiproliferative activity against the breast cancer cell line MCF-7. The most active compounds 3d, 3e, 3f, 5a and 5c were also evaluated for their ability to inhibit EGFR expression with reference to erlotinib. In silico studies using rigid docking, flexible docking and molecular dynamics were performed to explore the possibility of direct interactions between the active molecules and the ATP-binding site of EGFR. Most compounds demonstrated a potent cytotoxic activity against the MCF-7 cell line. The most active compounds 3d, 3e, 3f, 5a and 5c with IC50 values of 5, 26, 44, 20, and 50 nM, respectively, were further tested against HCT-116, HepG-2, A549 and SGC-7901 cell lines. All the tested compounds showed better activity than the reference standard drugs (doxorubicin and erlotinib) in all the tested cell lines. Compound 5a was the most potent one against HCT-116 with an IC50 value of 5 nM, while compound 3d was the most potent one against the breast cancer cell line MCF-7, liver HepG-2, lung A549 and the gastric cancer cell line SGC-7901 with IC50 values of 5, 77, 27 and 60 nM, respectively. Compounds 3d and 5a were tested for their cytotoxic effects on the normal breast cancer cell line MCF10a and their IC50 values were 35.78 and 22.77 mu M, respectively, indicating good selectivity. The most active compounds 3d, 3e, 3f, 5a and 5c exhibited percent reduction in EGFR level ranging from 80.9 to 88.0%. The apoptotic effect of compounds 3d and 5a on MCF-7 cells was investigated through cell cycle analysis. Both compounds showed increases in the number of cells in the pre-G1 phase of 14 and 22 folds, respectively, compared to the control. Both compounds exhibited total apoptosis of 28.06 and 43.88%, respectively. Docking of the new ligands revealed high scores compared to that of erlotinib. In the case of thiourea derivatives 3d and 3e, more stable hydrogen bonds via the thiourea group were demonstrated through molecular dynamics.
Pharmacophore based virtual screening for natural product database revealed possible inhibitors for SARS-COV-2 main protease
(Elsevier, 2022-05) El-Ashrey, Mohamed K; Bakr, Riham O.; Fayed, Marwa A.A; Refaey, Rana H; Nissan, Yassin M
The challenge continues globally triggered by the absence of an approved antiviral drug against COVID-19 virus infection necessitating global concerted efforts of scientists. Nature still provides a renewable source for drugs used to solve many health problems. The aim of this work is to provide new candidates from natural origin to overcome COVID-19 pandemic. A virtual screening of the natural compounds database (47,645 compounds) using structure-based pharmacophore model and molecular docking simulations reported eight hits from natural origin against SARS-CoV-2 main proteinase (Mpro) enzyme. The successful candidates were of terpenoidal nature including taxusabietane, Isoadenolin A & C, Xerophilusin B, Excisanin H, Macrocalin B and ponicidin, phytoconstituents isolated from family Lamiaceae and sharing a common ent-kaurane nucleus, were found to be the most successful candidates. This study suggested that the diterpene nucleus has a clear positive contribution which can represent a new opportunity in the development of SARS-CoV-2 main protease inhibitors
Synthesis and biological evaluation of new coumarin derivatives as cytotoxic agents
(wiley online library, 4/19/2021) Ragab, Fatma A; Eissa, Amal A. M; Fahim, Samar H; Salem, Mohammad A; Gamal, Mona A; Nissan, Yassin M
New coumarin derivatives 9a–f, 10a–e, and 11a–f were synthesized and evaluated for their cytotoxic activity against a human breast cancer cell line (MCF-7). All compounds exhibited good activity in the nanomolar range, using doxorubicin and erlotinib as positive controls. The most active compound 9d with IC50 of 21 nM was tested against the HCT-116, HepG-2, A549, and SGC-7901 cell lines, with IC50 values of 0.021, 0.170, 0.028, and 0.11 µM, respectively. Compound 9d was further investigated for its ability to suppress the expression of epidermal growth factor receptor (EGFR). Compound 9d decreased the concentration of EGFR by 87%, using erlotinib as a positive control. A docking study revealed similar or higher scores than for erlotinib and similar binding poses providing interactions with the hinge region of the tyrosine kinase (TK). Besides the effect on expression, this in silico investigation predicts the possibility of direct binding between the new coumarin derivatives and the EGFR TK. Moreover, computational calculation for ADME properties for the most active compounds 9d, 9e, 10c, and 11c revealed the expected high gastrointestinal tract absorption, moderate water solubility with no central nervous system toxicity, and druglikeness. © 2021 Deutsche Pharmazeutische Gesellschaft