Moussa, S. A., E. E. A. Osman, N. M. Eid, S. M. Abou-Seri, and S. M. El Moghazy, "Design and synthesis of novel 5-(4-chlorophenyl)furan derivatives with inhibitory activity on tubulin polymerization.", Future medicinal chemistry, vol. 10, issue 16, pp. 1907-1924, 2018 Aug 01. Abstract

AIM: Discovery of novel series of colchicine binding site inhibitors (CBSIs).

MATERIALS & METHODS: Isoxazoline 3a-d, pyrazoline 4a-b, 7a-f and 8a-f, cyclohexenone 9a-b and 10a-b or pyridine derivatives 11a-b were synthesized and evaluated for their inhibition of tubulin polymerization and cytotoxicity. Most of the compounds displayed potent to moderate antitumor activity against leukemia SR cell line.7c, 7e and 11a were more potent than colchicine with IC of 0.09, 0.05 and 0.06 μM, and percentage inhibition in tubulin polymerization of 95.2, 96.0 and 96.3%, respectively. Compounds 7c and 11a showed cell-cycle arrest at G2/M phase and induced apoptosis and were able to bind the colchicine binding site of tubulin with comparable affinity to colchicine. Docking study showed that these compounds may interact with tubulin exploiting a binding cavity not commonly reported in the binding of CBSI.

CONCLUSION: Compounds 7c and 11a may be considered as promising CBSI based on their excellent activity and favorable drug likeness profile.

Nowar, R. M., E. E. A. Osman, S. M. Abou-Seri, S. M. El Moghazy, and D. A. Abou El Ella, "Design, synthesis and biological evaluation of some novel quinazolinone derivatives as potent apoptotic inducers.", Future medicinal chemistry, vol. 10, issue 10, pp. 1191-1205, 2018 May 01. Abstract

AIM: Novel quinazolinone and triazinoquinazolinone derivatives were designed and synthesized as apoptotic inducers.

METHODOLOGY/RESULTS: Most of the synthesized compounds showed excellent antiproliferative activity against MCF-7 and HCT-116 cell lines, respectively. Compounds 7a, 8a, 8d, 14a and 14d were superior to doxorubicin as activators of caspases 3, 8 and 9 in HCT-116 cell line. The most potent caspase inducers, 8d and 14a showed cell cycle arrest mainly in G1 and S phase, respectively and increased the levels of p53, Bax and the Bax/Bcl-2 ratio compared with doxorubicin in HCT-116 cells with excellent selectivity against CCD-18Co human colon normal cell line.

CONCLUSION: The synthesized compounds can be considered as potent apoptotic inducers interfering with extrinsic and intrinsic apoptotic pathways.

Osman, E. E. A., "Analytical investigation of different mathematical approaches utilizing manipulation of ratio spectra.", Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy, vol. 188, pp. 469-477, 2018 Jan 05. Abstract

This work represents a comparative study of different approaches of manipulating ratio spectra, applied on a binary mixture of ciprofloxacin HCl and dexamethasone sodium phosphate co-formulated as ear drops. The proposed new spectrophotometric methods are: ratio difference spectrophotometric method (RDSM), amplitude center method (ACM), first derivative of the ratio spectra (1DD) and mean centering of ratio spectra (MCR). The proposed methods were checked using laboratory-prepared mixtures and were successfully applied for the analysis of pharmaceutical formulation containing the cited drugs. The proposed methods were validated according to the ICH guidelines. A comparative study was conducted between those methods regarding simplicity, limitations and sensitivity. The obtained results were statistically compared with those obtained from the reported HPLC method, showing no significant difference with respect to accuracy and precision.

Ahmed, R. I., E. E. A. Osman, F. M. Awadallah, and S. M. El-Moghazy, "Design, synthesis and molecular docking of novel diarylcyclohexenone and diarylindazole derivatives as tubulin polymerization inhibitors.", Journal of enzyme inhibition and medicinal chemistry, vol. 32, issue 1, pp. 176-188, 2017 Dec. Abstract

New target compounds were designed as inhibitors of tubulin polymerization relying on using two types of ring B models (cyclohexenone and indazole) to replace the central ring in colchicine. Different functional groups (R1) were attached to manipulate their physicochemical properties and/or their biological activity. The designed compounds were assessed for their antitumor activity on HCT-116 and MCF-7 cancer cell lines. Compounds 4b, 5e and 5f exhibited comparable or higher potency than colchicine against colon HCT-116 and MCF-7 tumor cells. The mechanism of the antitumor activity was investigated through evaluating the tubulin inhibition potential of the active compounds. Compounds 4b, 5e and 5f showed percentage inhibition of tubulin in both cell line homogenates ranging from 79.72% to 89.31%. Cell cycle analysis of compounds 4b, 5e and 5f revealed cell cycle arrest at G2/M phase. Molecular docking revealed the binding mode of these new compounds into the colchicine binding site of tubulin.[Formula: see text].

El-Moghazy, S. M., R. F. George, E. E. A. Osman, A. A. Elbatrawy, M. Kissova, A. Colombo, E. Crespan, and G. Maga, "Novel pyrazolo[3,4-d]pyrimidines as dual Src-Abl inhibitors active against mutant form of Abl and the leukemia K-562 cell line.", European journal of medicinal chemistry, vol. 123, pp. 1-13, 2016 Nov 10. Abstract

Some novel 6-substituted pyrazolo[3,4-d]pyrimidines 4, 5, 6a-d, 7a-c, 8 and pyrazolo[4,3-e][1,2,4]triazolo[4,3-a]pyrimidines 9a-c, 10a-c, 11, 12a,b, 13a-c and 14 were synthesized and characterized by spectral and elemental analyses. They were screened for their biological activity in vitro against Abl and Src kinases. Compounds 7a and 7b revealed the highest activity against both wild and mutant Abl kinases as well as the Src kinase and the leukemia K-562 cell line. They can be considered as new hits for further structural optimization to obtain better activity.