Browsing by Author "Kamal, Aliaa M"

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Design, synthesis and assessment of new series of quinazolinone derivatives as EGFR inhibitors along with their cytotoxic evaluation against MCF7 and A549 cancer cell lines
(Elsevier, 06/01/2021) Aziz, Marian W; Kamal, Aliaa M; Mohamed, Khaled O; Elgendy, Adel A
New acetamide (IV a-e) and 1,3-thiazolidinone derivatives (VII a-e) were designed, synthesized and assessed for their cytotoxic activity against MCF-7 and A549 cell lines along with their lead compounds (erlotinib and gefitinib). The newly designed compounds were prepared according to the adopted procedures in schemes 1 and 2 from their quinazolinone parents. 3D QSAR pharmacophore and docking molecular modeling protocols were conducted using Discovery Studio program, beside a full biological assay for these compounds. The cytotoxicity evaluation demonstrated that compounds IVb, IVc, VIIa, VIIb, VIId exhibited potent cytotoxic activities against both MCF-7 and A549 cell lines. Moreover, the molecular modeling studies corroborated to the affinity of the compounds towards EGFR. Consequently, these five compounds were then screened for their EGFR inhibition and evaluated as well for their toxicity to normal cells, which revealed that the acetamide derivative IVc and the thiazolidinone derivative VIIa were the most potent and least toxic. DNA flow cytometry analysis was conducted for compounds IVc and VIIa, which indicated that they both induced arrest at G2/M phase of the cell cycle
Development of potential anticancer agents and apoptotic inducers based on 4-aryl- 4H chromene scaffold: Design, synthesis, biological evaluation and insight on their proliferation inhibition mechanism
(Elsevier, 12/11/2021) Elshemy, Heba A. H; Zaki, Mohamed A; Mahmoud, Ayman M; Khan, Shabana I; Chittiboyina, Amar G; Kamal, Aliaa M
An array of 4-aryl-2-amino-4H chromene derivatives were designed, synthesized, and evaluated for cytotoxic activity against four cancer cell lines and two non-cancerous cell lines. The most active candidates were further screened for their in vitro anticancer activity on NCI panel of 60 human cancer cell lines where compounds 2a, 2b, 4a-2, and 2e showed promising activity against various leukemia, non-small lung, renal, prostate, and breast cancer cell lines, particularly against NCI-H522 non-small lung cancer cell line (GI50 of 0.35-0.60 µM), MCF7 breast cancer cell line (GI50 of 0.34-0.59 µM), and MDA-MB-468 breast cancer cell line (GI50 of 0.23-0.40 µM). Compound 2b was the most potent against all leukemia and prostate cancer cell lines with GI50 values (0.29-0.60 µM). Compound 2b inhibited the proliferation of MCF-7 and HepG2 cells by inducing cell cycle arrest and apopotosis. 2b downregulated the mRNA abundance of BAX, Apaf-1 and caspase-3 and upregulated BCL-2. The activities of caspase-3 and caspase-9 were declined in MCF-7 and HepG2 cells treated with compound 2b. Compounds 2b and 4a-2 inhibited tubulin polymerization, with an IC50 values of 0.92 and 1.13 µM, respectively. These findings indicate that these synthesized compounds may represent potential drug candidates to inhibit the proliferation of different types of cancer cells.
Development of Semisynthetic Apoptosis-Inducing Agents Based on Natural Phenolic Acids Scaffold: Design, Synthesis and In-Vitro Biological Evaluation
(Multidisciplinary Digital Publishing Institute (MDPI), 2022-10) Ezzat, Shahira M; Teba, Heba El Sayed; Shahin, Inas G; Hafez, Ahmed M; Kamal, Aliaa M; Aborehab, Nora M
: A crucial target in drug research is magnifying efficacy and decreasing toxicity. Therefore, using natural active constituents as precursors will enhance both safety and biological activities. Despite having many pharmacological activities, caffeic and ferulic acids showed limited clinical usage due to their poor bioavailability and fast elimination. Therefore, semisynthetic compounds from these two acids were prepared and screened as anticancer agents. In this study, CA and FA showed very potent anticancer activity against Caco-2 cells. Consequently, eighteen derivatives were tested against the same cell line. Four potent candidates were selected for determination of the selectivity index, where compound 10 revealed a high safety margin. Compound 10 represented a new scaffold and showed significant cytotoxic activity against Caco-2. Cell-cycle analysis and eval- uation of apoptosis showed that derivatives 10, 7, 11, 15 and 14 showed the highest proportion of cells in a late apoptotic stage. :