Design, synthesis and biological study of hybrid drug candidates of nitric oxide releasing cucurbitacin-inspired estrone analogs for treatment of hepatocellular carcinoma., Abou-Salim, Mahrous A., Shaaban Mohamed A., Abdelhameid Mohammed K., Elshaier Yaseen A. M. M., and Halaweish Fathi , Bioorganic chemistry, Volume 85, p.515-533, (2019) Abstractabou-salim2019.pdf

Development of hybrid drug candidates is well known strategy for designing antitumor agents. Herein, a novel class of nitric oxide donating cucurbitacin inspired estrone analogs (NO-CIEAs) were designed and synthesized as multitarget agents. Synthesized analogs were initially evaluated for their anti-hepatocellular carcinoma activities. Among the tested analogs, NO-CIEAs 17 and 20a exhibited more potent activity against HepG2 cells (IC = 4.69 and 12.5 µM, respectively) than the reference drug Erlotinib (IC = 25 µM). Interestingly, NO-CIEA 17 exerted also a high potent activity against Erlotinib-resistant HepG2 cell line (HepG2-R) (IC = 8.21 µM) giving insight about its importance in drug resistance therapy. Intracellular measurements of NO revealed that NO-CIEAs 17 and 20a showed a significant increase in NO production in tumor cells after 1 h of incubation comparable to the reference prodrug JS-K. Flow cytometric analysis showed that both NO-CIEAs 17 and 20a mainly arrested the HepG2 cells in the G0/G1 phase. Also, In-Cell Based ELISA screening showed that NO-CIEA 17 resulted in a potential inhibitory activity towards the EGFR and MAPK (25% and 29% inhibition compared to untreated control cells, respectively). This data suggests the binding ability of NO-CIEA 17 to the EGFR and ERK to be well correlated along with the docking and cellular studies. Also, treatment of HepG2-R cells with NO-CIEA 17 showed a potential reduction of MRP2 expression in a dose dependent manner providing a significant impact on the chemotherapeutic resistance. Overall, the current study provides a potential new approach for the discovery of a novel antitumor agent against HCC.

SYNTHESIS OF NOVEL ARYL SUBSTITUTED PYRAZOLO [3, 4-D] PYRIMIDINES AND THEIR EVALUATION AS CYTOTOXIC AGENTS, El-hamid, Mohammed Abd K. , International Journal of Chemical Science and Technology, Volume 1, Issue 4, p.126-140, (2011) hct_cell_line.pdf
Synthesis of certain fused pyrrolothieno[3, 2-e] pyrazine derivatives with possible anxiolytic activity, El-Hameid, Mohammed K.Abd , organic chemistry ,an indian journal , Volume 9, Issue 11, p.[427-436], (2013) 02_ocaij_org2634907.pdf
Synthesis, antimicrobial and cytotoxic activity of novel 4-phenoxy and 4-(substitutedamino) pyrazolo [3, 4-d] pyrimidine derivatives, Abdelhameid, Mohammed Kamal , organic chemistry an andian journal, Volume , 9, Issue 9, p. [350-362], (2013) 02_ocaij_org2634482.pdf
Design, synthesis and screening of 1, 2, 4-triazinone derivatives as potential antitumor agents with apoptosis inducing activity on MCF-7 breast cancer cell line, Abdelhameid, Mohammed K. , European Journal of Medicinal Chemistry, Volume 156, Issue 12, p.563e579, (2018) 5.pdf
Enhancement to synthesize, design and dock of novel EGFR inhibitors containing pyrazolo[3,4-d]pyrimidine cores of expected anticancer activity, K.Abdel-Hamid, Mohamed, M.Kandeel Manal, and Eman K. A. Abdelall , OCAIJ,, Volume 10, Issue 12, p.1181–1195, (2014) 2-.pdf
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