Browsing by Author "Abouzid, Khaled A. M"

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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.
Drug repurposing of pyrazolotriazine derivatives as potential anti-SARS-CoV-2 agents: in vitro and in silico studies
(BioMed Central Ltd, 2024-07) Oudah, Khulood H; Najm, Mazin A. A; Barghash, Reham F; Kutkat, Omnia; GabAllah, Mohamed; Albohy, Amgad; Abouzid, Khaled A. M
The search for new molecules targeting SARS-CoV-2 has been a priority since 2020. The continuous evolution of new mutants increases the need for more research in the area. One way to find new leads is to repurpose existing drugs and molecules against the required target. Here, we present the in vitro and in silico screening of ten previously synthesized and reported compounds as anti-COVID 19 agents. The compounds were screened in vitro against VERO-E6 cells to find their Cytotoxic Concentration (CC50) and their Inhibitory Concentration (IC50). Compounds 1, 2, and 5 revealed a promising anti-SARS-CoV-2 of (IC50 = 2.4, 11.2 and 2.8 µM), respectively while compounds 3 and 7 showed moderate activity of (IC50 = 17.8 and 26.1 µM) compared to Chloroquine which showed an IC50 of 24.9 µM. Among tested compounds, 1 showed the highest selectivity (CC50/IC50) of 192.8. Docking, molecular dynamics and ADME studies were done to investigate potential interactions between compounds and SARS-CoV-2 targets as well as to study the possibility of using them as lead compounds.