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2020
Elwaie, T. A., S. E. Abbas, E. I. Aly, R. F. George, H. Ali, N. Kraiouchkine, K. S. Abdelwahed, T. E. Fandy, K. A. El Sayed, Z. Y. Abd Elmageed, et al., "HER2 Kinase-Targeted Breast Cancer Therapy: Design, Synthesis, and and Evaluation of Novel Lapatinib Congeners as Selective and Potent HER2 Inhibitors with Favorable Metabolic Stability.", Journal of medicinal chemistry, vol. 63, issue 24, pp. 15906-15945, 2020. Abstract

HER2 kinase as a well-established target for breast cancer (BC) therapy is associated with aggressive clinical outcomes; thus, herein we present structural optimization for HER2-selective targeting. HER2 profiling of the developed derivatives demonstrated potent and selective inhibitions (IC: 5.4-12 nM) compared to lapatinib (IC: 95.5 nM). Favorably, exhibited minimum off-target kinase activation. NCI-5-dose screening revealed broad-spectrum activities (GI: 1.43-2.09 μM) and had a remarkable selectivity toward BC. Our compounds revealed significant selective and potent antiproliferative activities (∼20-fold) against HER2+ (AU565, BT474) compared to HER2(-) cells. At 0.1 IC, , , and inhibited pERK1/2 and pAkt by immunoblotting. Furthermore, demonstrated potent tumor regression against the BT474 xenograft model. Notably, a metastasis case was observed in the vehicle but not in the test mice groups. CD-1 mice metabolic stability assay revealed high stability and low intrinsic clearance of ( > 145 min and CL < 9.6 mL/min/kg).

2015
Awadallah, F. M., T. A. El-Waei, M. M. Hanna, S. E. Abbas, M. Ceruso, B. E. Oz, O. O. Guler, and C. T. Supuran, "Synthesis, carbonic anhydrase inhibition and cytotoxic activity of novel chromone-based sulfonamide derivatives.", European journal of medicinal chemistry, vol. 96, pp. 425-35, 2015. Abstractpaper.pdf

Four series of sulfonamides incorporating chromone moieties were synthesized and assessed for their cytotoxic activity against MCF-7 and A-549 cell lines, considering the fact that some of these tumors overexpress isoforms of carbonic anhydrase (CA, EC 4.2.1.1) which is inhibited by sulfonamides. Most new sulfonamides showed weak inhibitory activity against the offtarget, cytosolic isoforms hCA I, II but effectively inhibited the tumor-associated hCA IX and XII. The most active compounds featured a primary SO2NH2 group and were active in the low micromolar range against MCF-7 and A-549 cell lines. Compound 4a showed IC50 of 0.72 and 0.50 μM against MCF-7 and A-549 cell lines, respectively, and was further evaluated for its proapoptotic activity which proved enhanced in both tumor types.

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