Browsing by Author "Abd-Elhalim M.M."

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Cytotoxicity and gene expression profiles of novel synthesized steroid derivatives as chemotherapeutic anti-breast cancer agents
(2011) Elmegeed G.A.; Khalil W.K.B.; Mohareb R.M.; Ahmed H.H.; Abd-Elhalim M.M.; Elsayed G.H.; Hormones Department; National Research Centre; 12622 Dokki; Giza; Egypt; Cell Biology Department; National Research Centre; Dokki; Giza; Egypt; Organic Chemistry Department; Faculty of Pharmacy; October University of Modern Sciences and Arts (MSA); October City; Egypt; Chemistry Department; Faculty of Science; Cairo University; Cario; Egypt
Anti-cancer agents which combine two biologically active compounds in one such as steroidal heterocyclic derivatives attain both hormone and cytotoxic effects on cancer cells. The aim of the present study is to synthesize and evaluate new potential chemotherapeutic anti-breast cancer agents. Several pyridazino-, pyrimido-, quinazolo-, oxirano- and thiazolo-steroid derivatives were synthesized. The structure of the novel steroid derivatives was confirmed using the analytical and spectral data. The most structurally promising of the novel synthesized steroid derivatives, compounds 8, 12, 17, 20, 22c, 24c, 30a and 30b, were investigated individually as anti-breast cancer agents against human breast cancer cells (MCF-7) using sulforhodamine B (SRB) assay. The tested compounds 17, 20, 22c and 8 showed potent broad spectrum cytotoxic activity in vitro after 48 h incubation. Compound 17 (IC 50 = 2.5 ?M) exhibited more inhibitory influence on MCF-7 growth than the reference drug doxorubicin (Dox) (IC 50 = 4.5 ?M) after 48 h incubation. Also, the present study showed that all the tested steroid derivatives exhibited significant depletion with various intensities in gene expression of breast cancer related genes (VEGF, CYP19 and hAP-2?). Noteworthy, compounds 17, 20 and 22c showed the most pronounced effect in this respect. � 2011 Elsevier Ltd. All rights reserved.
Development of new indole-derived neuroprotective agents
(2011) Mohareb R.M.; Ahmed H.H.; Elmegeed G.A.; Abd-Elhalim M.M.; Shafic R.W.; Organic Chemistry Department; Faculty of Pharmacy; October University of Modern Sciences and Arts (MSA); October City; Egypt; Chemistry Department; Faculty of Science; Cairo University; Cario; Egypt; Hormones Department; National Research Centre; Dokki 12622; Cairo; Egypt
There is a great deal of interest in neurotrophin therapy to prevent neuronal degeneration. The present study aimed at synthesizing new functionalized indole derivatives with structures justifying neuroprotective activity using l-tryptophan (TRP)� as starting material. The potential neuroprotective effect of these newly synthesized agents against acrylamide (ACR) induced neurotoxicity was investigated in adult female rats. The novel indole derivatives, indolylmethyl pyridine derivatives 9a,b, pyrimidinylindolyl propanone derivatives 12a-c, pyrazolylindolyl propanone derivatives 14a,b, and indolyl tetrazolopropanoic acid derivative 17 were synthesized and their chemical structures were confirmed by studying their analytical and spectral data. The administration of ACR [ip, 50 mg kg -1 body weight (b. wt.)] alone resulted in significant increase in brain malondialdehyde level (MDA) and lactate dehydrogenase (LDH) activity whereas it caused significant decrease in brain monoamines levels and antioxidant enzymes activity. Treatment with the indole derivatives 9b, 12c, 14a, and 17 (ip, 50 mg kg-1 b. wt.) prior to ACR produced neuroprotective activity with various intensities depending on the structure of each compound. Compound 17 in which the tetrazole ring was attached to the TRP moiety ranked as the strongest neuroprotective agent. All the tested compounds have been shown to possess antioxidant properties offering promising efficacy against oxidative stress induced by ACR administration. � 2011 Elsevier Ltd. All rights reserved.