Browsing by Author "Mohareb R.M."

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Anti-tumor and anti-leishmanial evaluations of 1,3,4-oxadiazine, pyran derivatives derived from cross-coupling reactions of ?-bromo-6H-1,3,4- oxadiazine derivatives
(2011) Mohareb R.M.; Schatz J.; Faculty of Pharmacy; Organic Chemistry Department; October University for Modern Science and Arts University; El-Wahaat Road; October City; Egypt; Department of Chemistry; Faculty of Science; Cairo University; Giza; A.R.; Egypt; Department Chemie und Pharmazie - Organische Chemie i; Friedrich-Alexander-Universit�t Erlangen-N�rnberg; Henkestra�e 42; D-91054 Erlangen; Germany
Cyanoacetylhydrazine reacted with the ?-bromoacetophenones 2a,b to give hydrazide-hydrazone derivatives 3a,b. The latter products were cyclized to the 1,3,4-oxadiazine derivatives 4a,b. Bromination of the latter products gave the 6-bromo-6H-1,3,4-oxadiazine derivatives 5a,b which underwent a series of cross-coupling reactions. The antitumor evaluation of the newly synthesized products against the three cancer cells namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) showed that some of them have high inhibitory effect towards three cell lines which is higher than the standard. Moreover, the anti-leishmanial activity of the newly synthesized product was tested on Leishmania donovani amastigotes showed that some compounds have high activity. � 2011 Published by Elsevier Ltd. All rights reserved.
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.
Design and synthesis of novel antimicrobial acyclic and heterocyclic dyes and their precursors for dyeing and/or textile finishing based on 2-n-acylamino-4,5,6,7-tetrahydrobenzo[b]thiophene systems
(2011) Shams H.Z.; Mohareb R.M.; Helal M.H.; Mahmoud A.E.-S.; Department of Chemistry; Faculty of Science; Helwan University; P.O. 11790; Ain Helwan; Cairo; Egypt; Department of Organic Chemistry; Faculty of Pharmacy; October University for Modern Sciences and Arts; P.O. 12613; October City; Egypt; Department of Chemistry; Faculty of Science; Cairo University; Giza; P.O. 12311; Egypt
A series of novel polyfunctionalized acyclic and heterocyclic dye precursors and their respective azo (hydrazone) counterpart dyes and dye precursors based on conjugate enaminones and/or enaminonitrile moieties were synthesized. The dyes and their precursors are based on 2-cyano-N-(3-cyano-4,5, 6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide, 2-ethoxycarbonyl-N-(3-cyano-4,5, 6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide or 2-phenylcarbamoyl-N-(3-cyano- 4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide systems as precursors. The latter compounds were used to synthesize polyfunctional thiophene-, thiazole-, pyrazole, pyridine-, pyrimidine-, oxazine-, as well as acyclic moieties. The dyes and dye precursors were characterized by elemental analysis and spectral methods. All dyes and their precursors were screened in vitro and evaluated for both their antibacterial and antifungal activities. MIC data of the novel dye systems and their respective precursors showed significant antimicrobial activity against most tested organisms. Some compounds exhibited comparable or even higher efficiency than selected standards. Dyes were applied at 5% depth for disperse dyeing of nylon, acetate and polyester fabrics. Their spectral characteristics and fastness properties were measured and evaluated.
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.
New approaches for the uses of cyclohexan-1,4-dione for the synthesis of 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-b]pyridine derivatives used as potential anti-prostate cancer agents and pim-1 Kinase inhibitors
(Bentham Science Publishers B.V., 2018) Mohareb R.M.; Abdo N.Y.M.; El-Sharkawy K.A.; Department of Chemistry; Faculty of Science; Cairo University; Giza; Egypt; Chemistry Department; Faculty of Education; Alexandria University; Alexandria; 21526; Egypt; Department of Pharmaceutical Chemistry; College of Pharmacy; Jazan University; P.O. Box 114; Jazan; 45142; Saudi Arabia; Department of Chemistry; Faculty of Biotechnology; October University for Modern Sciences and Arts (MSA); El-Wahat Road; 6th October City; Cairo; Egypt
Background: Among the wide range of heterocycles, tetrahydrobenzothienopyridine derivatives acquired a special attention due to their wide range of pharmacological activities especially the therapeutic activities. Many pharmacological drugs containing the thiophene nucleus were known in the market. Method: A series of tetrahydrobenzothienopyridine derivatives were synthesized from the reaction of 2-amino- 3-benzoyl-4,5-dihydrobenzo[b]thiophen-6(7H)-one, synthesized and used for further heterocyclization reactions through reaction with different reagents. Results: Antiproliferative evaluations and c-Met kinase, Pim-1 kinase inhibitions were performed where some compounds revealed high activities. Conclusion: The inhibition of the newly synthesized compounds towards c-Met kinase, the five c-Metdependent cancer cell lines (A549, HT-29, MKN-45, U87MG, and SMMC-7721) and one c-Met-independent cancer cell line (H460) were investigated using foretinib as a standard drug. The results showed that compounds 6b, 7e, 9b, 9e, 16c and 20d were more active than foretinib. Furthermore, compounds 6b, 13b, 16b and 16c were selected to examine their Pim-1 kinase inhibition activity, where compounds 16b and 16c were of high potencies with IC50 values of 0.28 and 0.32 ?M, while compounds 6b and 13b were less effective (IC50 > 10 ?M). � 2018 Bentham Science Publishers.
Novel synthesis and antitumor evaluation of polyfunctionally substituted heterocyclic compounds derived from 2-cyano-N-(3-cyano-4,5,6,7- tetrahydrobenzo[b]thiophen-2-yl)-acetamide
(2011) Shams H.Z.; Mohareb R.M.; Helal M.H.; Mahmoud A.E.; Department of Chemistry; Faculty of Science; Helwan University; Ain Helwan; Cairo; Egypt; Department of Organic Chemistry; Faculty of Pharmacy; October University for Modern Sciences and Arts; October City; Egypt; Department of Chemistry; Faculty of Science; Cairo University; Giza; Egypt
The reaction of 2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene with ethyl cyanoacetate gave 2-cyano-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2- yl)-acetamide. The latter was used to synthesize different heterocyclic derivatives comprising thiophene, thiazole, pyrazole, pyridine, pyrimidine, and coumarin rings. The mechanistic and synthetic pathways depended on regioselective attack and/or cyclization by the cyanoacetamido moiety in the key precursor on various chemical reagents. The competition of the reaction pathways including dipolar cyclization, dinucleophilic-bielectrophilic attack, ?-attack, Gewald-type attack, and condensation reactions led to the diversity of the synthesized products. The antitumor activities of the synthesized products were studied and evaluated. Most of the compounds revealed high inhibitory effects when screened in vitro for their antiproliferative activity. Three human cancer cell lines, namely, breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) were used in the screening tests. The simplicity of the synthetic procedures which mainly involved one-pot reactions under mild reaction conditions, the convenience of yield production and the diversity of the reactive sites in the produced systems play a valuable role for further heterocyclic transformations and further biological investigations. � 2010 by the authors.
Novel synthesis of hydrazide-hydrazone derivatives and their utilization in the synthesis of coumarin, pyridine, thiazole and thiophene derivatives with antitumor activity
(2011) Mohareb R.M.; Fleita D.H.; Sakka O.K.; Department of Organic Chemistry; Faculty of Pharmacy; October University for Modern Sciences and Arts; October City; AR; Egypt; Department of Chemistry; Faculty of Science; Cairo University; Giza; AR; Egypt; Department of Chemistry; Faculty of Science; American University in Cairo; 5th Settlement; AR; Egypt
The reaction of cyanoacetyl hydrazine (1) with 3-acetylpyridine (2) gave the hydrazide-hydrazone derivative 3. The latter compound undergoes a series of heterocyclization reactions to give new heterocyclic compounds. The antitumor evaluation of the newly synthesized products against three cancer cell lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) was performed. Most of the synthesized compounds showed high inhibitory effects. � 2010 by the authors.
The reaction of cyanoacetic acid hydrazide with 2-acetylfuran: Synthesis of coumarin, pyridine, thiophene and thiazole derivatives with potential antimicrobial activities
(2009) Mohareb R.M.; El-Arab E.E.; El-Sharkawy K.A.; Faculty of Pharmacy; October University for Modern Sciences and Arts; Elwahaat Road; October City; Egypt; Faulty of Science; Chemistry Department; Cairo University; Egypt; National Organization of Drug Control and Research (NODCAR); P.O. 29; Cairo; Egypt
The hydrazide-hydrazone derivative 1 was formed through the reaction of cyanoacetic acid hydrazide with 2-acetylfuran. Compound 1 underwent a series of hetrocyclization reactions through its reaction with different chemical reagents to produce arylidene, coumarin, aryl hydrazone, pyridine, thiophene and thiazole derivatives 2-10. The MIC values for the newly synthesized products were tested against E. coli, B. cereus, B. subtilis and C. albicans compared with ampicilline and cycloheximide as reference drugs. � Mohareb et al.; licensee �sterreichische Apotheker-Verlagsgesellschaft m. b. H.
The Reaction of Cyanoacetylhydrazine with ω-Bromo(4-methyl)acetophenone: Synthesis of Heterocyclic Derivatives with Antitumor Activity
(2010) Mohareb R.M.; Mohamed A.A.; Department of Organic Chemistry; Faculty of Pharmacy; October University for Modern Sciences and Arts; October City; AR; Egypt; Department of Chemistry; Faculty of Science; Cairo University; Giza; AR; Egypt; National Organization for Drug Control and Research (NODCAR); P.O. 29; Cairo; Egypt
New approaches for the synthesis of hydrazide-hydrazone derivatives were demonstrated as well as some heterocyclizations of such derivatives to afford 1,3,4-triazine, pyridine and 1,3,4-oxadiazine derivatives. The antitumor evaluation of the newly synthesized products against three cancer cell lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) were recorded. Most of the synthesized compounds showed high inhibitory effects. � 2010 by the authors.
The reaction of cyclohexan-1,3-dione with cyanomethylenes: Synthesis of thiophenes and their fused derivatives with antifungal activities
(2009) Mohareb R.M.; Sherif S.M.; Moustafa H.E.-D.; Department of Organic Chemistry; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA); El-Wahaat Road; October; A. R.; Egypt; Department of Chemistry; Faculty of Science; Cairo University; Giza; A. R.; Egypt
2-Amino-7-oxotetrahydrobenzo[b]thiophenes 3a,b were prepared according to the Gewald procedure. Their reactivity toward a variety of chemical reagents was studied to give annulated heterocycles with potential bio-responses.
The reaction of β-amino-α,γ-dicyanocrotononitrile with acetophenone: Synthesis of pyridine, pyridazine and thiophene derivatives with antimicrobial activities
(2008) Mohareb R.M.; El-Sharkawy K.A.; Sherif S.M.; Department of Chemistry; Faculty of Science; Cairo University; Giza; Egypt; Department of Organic Chemistry; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA); October; Egypt
Condensation of ?-amino-?,?-dicyanocrotononitrile (1) with acetophenone gave 2-amino-4-phenylpenta-1,3-diene-1,1,3-tricarbonitrile (2). The latter product was used in a series of heterocyclization reactions with different reagents such as diazonium salts, hydrazines, hydroxylamines and elemental sulfur to give pyridazine, pyrazole, isoxazole and thiophene derivatives, respectively. On the other hand, it gave pyridine derivatives with aromatic aldehydes folowed by reaction with cyanomethylene reagents. The MIC values for the newly synthesized product were measured against E. coli, B. cereus, B. subtilis and C. albicans.
Synthesis and Application of Novel Reactive Disperse Dye Based on Tetrahydrobenzo[b] Thiophene Moiety
(Emerald Group Publishing Ltd., 2014) Mohamed F.A.; Mohareb R.M.; Textile Research Division; National Research Centre; Dokki; Giza; 12622; Egypt; Chemistry Departments; Faculty of Science; Cairo University; Giza; Egypt; Faculty of Pharmacy; October University for Modern Science & Arts (MSA); Elwahaat Road; October City; Giza; Egypt
Ethyl 2-diazo-4, 5, 6, 7-tetrahydrobenzo[b] thiophene-3-carboxylate is reacted with malononitrile to give a hydrazone derivative. The latter product is reacted with 1-diazobenzene-4-?-sulphatoethylsulphone (PABSES) to give a disperse dye. The dye is synthesised by diazotisation and coupling reactions. First, it is synthesised with the chromophoric moiety of ethyl 2-hydrazomalononitrilo-4,5,6,7-tetrahydrobenzo[b] thiopheen- 3-carboxylate and coupled with diazonium salts that have the aforementioned reactive groups, thus yielding the new target reactive. The synthesised dye is applied onto wool, polyester and wool-polyester (blend) fabrics under typical exhaust dyeing conditions and their dyeing properties are investigated. The structure of this dye is characterised and confirmed by melting point, elemental analysis, infrared, ultraviolet-visible spectroscopy (UV/VIS) and nuclear magnetic resonance ( 1 H-NMR) data. The dyeing of polyester, wool and polyester/wool blend fabrics with a reactive disperse dye gives very good build up and fastness properties by using a nonionic vinylsulphone (VS) derivative, which increases the substantivity of the dye towards wool fabric. Maximum exhaustion as well as total fixation efficiency by using a sulfatoethylsulfone (SES)-based dye on wool fabric is achieved at a neutral pH of 7. This feature of the dye structure significantly improves the union dyeing of wool/polyester blend fabrics with very good build up and fastness properties. � 2014 Emerald Group Publishing Limited.
Synthesis and E/Z configuration determination of novel derivatives of 3-Aryl-2-(benzothiazol-2-ylthio) acrylonitrile, 3-(benzothiazol-2- ylthio)-4-(furan-2-yl)-3-buten-2-one and 2-(1-(Furan-2-yl)-3-oxobut-1-en-2-ylthio)-3-phenylquinazolin- 4(3H)-one
(American Society for Microbiology, 2011) Al-Omran F.; Mohareb R.M.; El-Khair A.A.; Ramadan, E., Department of Biology, School of Sciences and Engineering, The American University in Cairo, New Cairo, Egypt, Faculty of Pharmacy, Department of Pharmacology and Biochemistry, The British University in Egypt, El-Sherouk City, Egypt; Maged, M., Department of Biology, School of Sciences and Engineering, The American University in Cairo, New Cairo, Egypt, Faculty of Biotechnology, October University for Modern Sciences and Arts, Cairo, Egypt; Hosseiny, A.E., Department of Biology, School of Sciences and Engineering, The American University in Cairo, New Cairo, Egypt; Chambergo, F.S., Escola de Artes Cincias e Humanidades, Universidade de So Paulo, So Paulo, Brazil; Setubal, J.C., Instituto de Qumica, Universidade de So Paulo, So Paulo, Brazil; Dorry, H.E., Department of Biology, School of Sciences and Engineering, The American University in Cairo, New Cairo, Egypt
The hypersaline Kebrit Deep brine pool in the Red Sea is characterized by high levels of toxic heavy metals. Here, we describe two structurally related mercuric reductases (MerAs) from this site which were expressed in Escherichia coli. Sequence similarities suggest that both genes are derived from proteobacteria, most likely the Betaproteobacteria or Gammaproteobacteria. We show that one of the enzymes (K35NH) is strongly inhibited by NaCl, while the other (K09H) is activated in a NaCl-dependent manner. We infer from this difference that the two forms might support the detoxification of mercury in bacterial microorganisms that employ the compatible solutes and salt-in strategies, respectively. Three-dimensional structure modeling shows that all amino acid substitutions unique to each type are located outside the domain responsible for formation of the active MerA homodimer, and the vast majority of these are found on the surface of the molecule. Moreover, K09H exhibits the predominance of acidic over hydrophobic side chains that is typical of halophilic salt-dependent proteins. These findings enhance our understanding of how selection pressures imposed by two environmental stressors have endowed MerA enzymes with catalytic properties that can potentially function in microorganisms that utilize distinct mechanisms for osmotic balance in hypersaline environments. 2019 American Society for Microbiology. All Rights Reserved.
Synthesis of hydrazide-hydrazone derivatives and their evaluation of antidepressant, sedative and analgesic agents
(2010) Mohareb R.M.; El-Sharkawy K.A.; Hussein M.M.; El-Sehrawi H.M.; Faculty of Pharmacy; Organic Chemistry Department; October University for Modern Sciences and Arts (MSA); El-Wahat Road; 6 October City; Egypt; Department of Chemistry; Faculty of Science; Cairo University; Giza; A. R; Egypt; Faculty of Pharmacy (Girls); Pharmaceutical Chemistry Department; Al-Azhar University; Nasr City; Cairo; A. R; Egypt
The reaction of cyanoacetylhydrazine (1) with ?-bromo(4-methoxyacetophenone) (2) gave the hydrazide-hydrazone derivative 3. Compound 3 reacted with either potassium cyanide or potassium thiocyanide to give the cyanide or thiocyanide derivatives 4a or 4b respectively. The reaction of compound 3 with either hydrazine hydrate or phenylhydrazine gave the hydrazine derivatives 6a or 6b respectively. The latter compounds underwent a series of heterocyclization when react with different reagents to give 1,3,4-triazine and pyridine derivatives. The antidepressant, sedative and analgesic activities of the newly synthesized products were evaluated.
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.
Synthesis of progesterone heterocyclic derivatives of potential antimicrobial activity
(2008) Mohareb R.M.; Hana H.Y.; Department of Organic Chemistry; Faculty of Pharmacy; University of Modern Sciences and Arts (MSA); October City; Giza; Egypt; Hormone Department; National Research Centre; Dokki; Giza; Egypt
The aim of this work was to synthesize steroidal heterocycles and to elucidate the potential role of these compounds as antimicrobial agents. The synthesis of steroidal heterocycles containing the pyrazole, isoxazole, thiazole, pyrane, pyridine, pyridazine, or benzopyrane ring attached to the pregnene nucleus is reported. Progesterone (1) reacts with dimethyl formamide dimethyl acetal to form enamine 2. Heterocyclization of 2 with hydrazines, hydroxylamine, glycine, ethyl acetoacetate or cyanomethylene afforded novel steroidal heterocyclic derivatives. The in vitro antimicrobial evaluation showed that all synthesized compounds show activity against the used strains of Gram positive bacteria and fungi.
Uses of cyanoacetylhydrazine in heterocyclic synthesis: Novel synthesis of pyrazole derivatives with anti-tumor activities
(2012) Mohareb R.M.; El-Sayed N.N.E.; Abdelaziz M.A.; Departrment of Chemistry; Faculty of Science; Cairo University; Giza 12613; Egypt; Department of Organic Chemistry; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA); El-Wahaat Road; October City; Giza 12411; Egypt; National Organization for Drug Control and Research; P.O. Box 29; Cairo 11421; Egypt; College of Science; Department of Chemistry; King Saud University; Riyadh 11932; Saudi Arabia; Preparatory Year Department; AL-Ghad International Colleges for Health Sciences; Tabuk Male; Tabuk 41321; Saudi Arabia; Basic Science Department; Modern Academy for Engineering and Technology in Maadi; Maadi 11431; Cairo; Egypt
The reaction of cyanoacetylhydrazine with chloroacetyl chloride gave N?-(2-chloroacetyl)-2-cyanoacetohydrazide. The latter underwent cyclization to afford 1-(5 amino-3-hydroxy-1H-pyrazol-1-yl)-2-chloroethanone, which underwent nucleophilic substitution to give 3-(5-amino-3-hydroxy-1H- pyrazol-1-yl)-3-oxopropanenitrile. The latter two compounds were used as key synthons to synthesize new thiophene, pyran, thiazole and some fused heterocyclic derivatives. The antitumor activity of the newly synthesized compounds was evaluated against three human tumor cells lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) and some of these compounds were found to exhibit much higher inhibitory effects towards the three tumor cell lines than the Gram positive control doxorubicin. � 2012 by the authors.