Browsing by Author "Elmegeed G.A."

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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.
Evaluation of anti-inflammatory, anti-nociceptive, and anti-ulcerogenic activities of novel synthesized thiazolyl and pyrrolyl steroids
(2011) Mohareb R.M.; Elmegeed G.A.; Baiuomy A.R.; Eskander E.F.; William M.G.; Organic Chemistry Department; Faculty of Pharmacy; October University of Modern Sciences and Arts (MSA); Elwahaat Road; October City; Egypt; Chemistry Department; Faculty of Science; Cairo University; Cario; Egypt; Hormones Department; National Research Centre; 12622 Dokki; Cairo; Egypt; Pharmacology Department; National Research Centre; Dokki; Cairo; Egypt; Faculty of Medicine and Medical Sciences; Taif University; Saudi Arabia
Developing new therapeutic agents that can overcome gastrointestinal injury and at the same time could lead to an enhanced anti-inflammatory effect becomes an urgent need for inflammation patients. Thiazolyl and pyrrolyl steroids were synthesized via straight forward and efficient methods and their structures were established based on their correct elemental analysis and compatible IR, 1H-NMR, 13C-NMR, and mass spectral data. The dihydrothiazolyl-hydrazonoprogesterone 12 and the aminopyrrolylprogesterone 16a showed anti-inflammatory, antinociceptive, and anti-ulcerogenic activity with various intensities. Edema were significantly reduced by both doses of tested compounds (25 and 50 mg/kg) at 2, 3, and 4 h post-carrageenan. The high dose of compound 16a was the most effective in alleviating thermal pain. Gastric mucosal lesions, caused in the rats by the administration of ethanol or indomethacin (IND), were significantly inhibited by each of the two tested compounds. These results provide a unique opportunity to develop new anti-inflammatory drugs which devoid the ulcerogenic liabilities associated with currently marketed drugs. Novel steroid hybrids incorporating the pyrrole or thiazole moiety through different linkages have been developed. The modified steroids 12 and 16a showed anti-inflammatory, anti-nociceptive, and/or non-ulcerogenic activities. These encouraging results may be of interest for finding new potent prescriptions. Copyright � 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Synthesis of modified steroids as a novel class of non-ulcerogenic, anti-inflammatory and anti-nociceptive agents
(2011) Mohareb R.M.; Elmegeed G.A.; Abdel-Salam O.M.E.; Doss S.H.; William M.G.; Organic Chemistry Department; Faculty of Pharmacy; October University of Modern Sciences and Arts (MSA); Elwahaat Road; October City; Egypt; Chemistry Department; Faculty of Science; Cairo University; Cario; Egypt; Hormones Department; National Research Centre; 12622 Dokki; Cairo; Egypt; Toxicology and Narcotics Department; National Research Centre; 12622 Dokki; Cairo; Egypt
The identification of compounds able to treat both pain and inflammation with limited side effects is one of the prominent goals in biomedical research. This study aimed at the synthesis of new modified steroids with structures justifying non-ulcerogenic, anti-inflammatory and anti-nociceptive activities. The steroid derivatives were synthesized via straightforward and efficient methods and their structures were established based on the analytical and spectral data. The in vivo anti-inflammatory, anti-nociceptive and anti-ulcerogenic activities of some of these compounds were studied. The newly synthesized compounds 8b, 19b, 24 and 31a showed anti-inflammatory, anti-nociceptive and anti-ulcerogenic activity with various intensities. Oedema was significantly reduced by either dose 25 or 50 mg/kg of all tested compounds at 3 and 4 h post-carrageenan. Compound 19b was the most effective in alleviating thermal pain. The analgesic activity of either dose of the compounds 8b, 24, 31a as well as the high dose 19b was significantly higher than that for indomethacin (IND). Gastric mucosal lesions caused in the rats by the administration of 96% EtOH and IND were inhibited by all tested compounds administered at (50 mg/kg) dose in the study. � 2011 Elsevier Inc. All rights reserved.
Synthesis of novel tryptophan derivatives of potential biological activity
(2009) Mohareb R.M.; Louca N.A.; Elmegeed G.A.; Hana H.Y.; Departament of Organic Chemistry; Faculty of Pharmacy; October University for Modem Sciences and Arts (MSA); El-Wahaat Road; October City; Egypt; Chemistry Department; Faculty of Science; Cairo University; Giza; Egypt; Hormone Department; National Research Centre; Dokki; Giza; Egypt
Tryptophan methyl ester 2 reacts with ethyl cyanoacetate to form acetonitrilocarbonyltryptophan methylester 3. The latter reacts with cyanomethylene reagents, hydrazines, cyanomethylenes and sulfur to form the corresponding ?-pyrido-3-indolopropanoate derivatives 6a,b, pyrazolyltryptophan methyl ester derivatives 8a,b and thiophenotryptophan methyl ester derivatives 10a,b, respectively. Also compound 3 reacts with benzaldehyde to give the condensated product 12. The reactivity of the latter product towards chemical reagents was studied to form pyridine, pyrazole and isoxazole derivatives.