Vol. 30, July, 2009.

contre indication levitra 1/30 SYNTHESIS AND ANTIOXIDANT ACTIVITY OF NOVEL INDOLE HETEROCYCLES

Mohamed M. Said , Nagat Ghareb, *Pierre Hanna and **Adel A. El-Gendy

Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University, Egypt.

*Pharmaceutics Department, Faculty of Pharmacy, Suez Canal University, Egypt.

**Organic Chemistry Department, Faculty of Pharmacy, Misr International University, Egypt.

Reaction of thiosemicarbazide and semicarbazide derivatives pasteque effet viagra 6a-h with cyclizing reagents such as ethyl-2-chloroacetate, ethyl-3-chloropropionate and ethyl-2-chloropropionate gave N-(3-substituted-5-oxo-2(oxo/thioxo)imidazolidin-1-yl)-5-halo-1-substituted-1H-indole-2-carboxamides site francais pour commander du viagra 7a-h, N-(3-substituted-6-oxo-2-(oxo/ thioxo)tetrahydropyrimidin-1(2H)-yl)-5-halo -1- substituted -1H-indole-2-carboxamides quel sont les effet du kamagra 8a-h and N-(3-substituted-4-methyl-5-oxo-2-(oxo /thioxo)imidazolidin-1-yl)-5-halo-1-substituted-1H-indole-2-carboxamides ou acheter du viagra en tunisie 9a-h respectively. While cyclocondensation of dosage viagra en ligne 6a-h with 3N sodium hydroxide gave 4-substituted-3-(5-halo-1-substituted-1H-indol-2-yl)-1H-1,2,4-triazole-5(4H)-(ones/thiones) viagra et accoutumance 10a-h. Also, cyclization of compounds a quel age prendre du cialis 6a-h with p-toluene sulphonic acid gave N-subsituted-5-(5-halo-1-substituted-1H-indol-2-yl)-1, 3, 4-(oxa/thia) diazol-2-amines prendre du viagra sans en avoir besoin 11a-h. 1-Substituted-5-halo-1H-indole-2-carbohydrazides risque prise cialis 5a-c whose refluxing with ethyl orthoformate in DMF gave 8-halo-[1,2,4]triazino[4,5-a]indol-1(2H)-ones 12a-c . Treatment of 12a-c with chloroacetyl chloride in presence of DMF/ Triethylamine gave 2-(2-chloroacetyl)-8-halo-[1,2,4]triazino[4,5-a]indol-1(2H)-ones 13a-c which were subsequently reacted with N-substituted piperazine to produce 8-halo-2-(2-(4-alkylpiperazin-1-yl)acetyl)-[1,2,4]triazino[4,5-a]indol-1(2H)-ones 14a-d. Ethyl 2-(5-benzyl-4-oxo-4,5-dihydro-3H-pyridazino[4,5-b]indol-3-yl)acetate 16 was cyclized to 12-benzyl-4, 4a-dihydro-2H-indolo [3, 2-d]-2H-pyridazino [6,1-c][1,2,4]triazin-3(4H)-one 17 by the action of hydrazine hydrate. The antioxidant activities were tested in vitro using DPPH radical scavenging assay.

2/30 IN VITRO AND IN VIVO CHARACTERISTICS OF SUSTAINED RELEASE ROSIGLITAZONE LIPID-MATRIX TABLETS

Ghada Abdelbary*

Department of Pharmaceuticsand Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

A sustained release lipid-matrix tablet formulation for oral antidiabetic drug; rosiglitazone maleate (RGZ) was designed and developed to achieve a 24 h release profile. Controlling the release of RGZ is particularly useful especially for achieving controlled plasma level of the drug, which would consequently decrease the side effects that occur in the case of conventional dosage forms. Using Compritol 888 ATO and Precirol 5 ATO as inert matrix-forming agents to control the release of RGZ, in the formulation tablets containing the physical mixtures or solid dispersions were investigated. The lipid-matrix tablets for these formulations were prepared by direct compression and their in vitro release tests were carried out. The release data was analyzed using various kinetic models in order to gain insight of the drug release mechanism. The solid dispersion based lipid-matrix tablets were found to be more effective than those compressed from physical mixtures in extending the release of RGZ. Scanning electron micrographs of the tablet surface and cross-section revealed the formed pores and channels in the matrices. Results of the release studies demonstrated that formula F15 (containing solid dispersion of drug : Precirol® 5 ATO ratio 1:2) extended drug release and fitted the theoretical target release profile. Most formulae exhibited Fickian diffusion drug release profiles. Upon in vivo comparison to the immediate release Avandia® tablet, the duration of effective RGZ therapeutic concentration from formula F15, in six healthy human volunteers, was significantly (P < 0.05) extended, thus lowering the potential of occurrence of side

 

 

3/30 SYNTHESIS OF BIOLOGICALLY ACTIVE COMPOUNDS BASED ON INDOLE-2-CARBOXYLATE SCAFFOLD

Mohamed M.A. Said, Marwa A. El-Metwaly, *Mohy El-Dein Abd el-fattah and **Adel A. El-Gendy.

Organic Chemistry Department, Faculty of Pharmacy, Suez-Canal University, Ismailia, Egypt, *Organic Chemistry Department, Faculty of Science, Suez-Canal University, Ismailia, Egypt and **Organic Chemistry Department, Faculty of Pharmacy, Misr International University, Cairo, Egypt

The VilsmeierHack formulation of ethyl 1H-indole-2-carboxylate (I) gave ethyl 3-formyl-1H-indole-2-carboxylate (II). Condensation of (II) with thiosemicarbazide gave thiosemicarbazone (III). imidazoline (IV) and thiazolidine (VII) were obtained through condensation of (III) with chloroacetic acid under different conditions. Compounds (IV) and (VII) on condensation with aromatic aldehydes afforded the corresponding arylidene drivatives (Va-d) and (VIIIa-d) respectively. Refluxing (IV) with ethyl chloroacetate, ethyl chloropropionate, benzyl chloride and methyl iodide furnished S-alkylated derivatives (VIa-d). Compounds (VIIIa–d) were also cyclized with hydroxylamine hydrochloride to yield compounds (IXa–d). The pharmacological and antimicrobial activities of certain new compounds were carried out.

 

 

4/30 MICROBIOLOGICAL ENVIRONMENTAL MONITORING OF A CLEAN ROOM IN A PHARMACEUTICAL PRODUCTION FACILITY IN EGYPT

Lamia F. Gebril*, Amal E. Ali**and Abd El Gawad Hashim**

**Department of Microbiology and Immunology, Faculty of Pharmacy,

Cairo University, Cairo, Egypt.

*The Holding Company for Biological Products and Vaccines (VACSERA)

An environmental monitoring (EM) program was implemented in a clean room of a pharmaceutical facility in Egypt as an overall assessment of the cleaning and sanitization practices adopted in the clean room. EM program involved air, surface and personnel monitoring of the filling area during regular production days. Results of active and passive air monitoring revealed an alert level of 12.8% with the highest level of contamination found in the autoclave room and high traffic areas. Hot spots eliciting action levels were those of high personnel interventions such as intercom and filling machine panel and were identified by surface monitoring. Class B showed higher alert level than class A both in air and surface monitoring. Personnel monitoring showed that the more used hand of the operator had the higher microbial contamination than the other hand and that personnel training and educational level had an impact on the environmental monitoring results. Isolated microorganisms during EM were Staphylococcus hominis, Staphylococcus saprophyticus, Staphylococcus epidermidis, Staphylococcus heamolyticus and Staphylococcus capitis. No fungi were isolated. These results emphasize the importance of EM program to provide information on the quality of aseptic processing environment in pharmaceutical industries and to identify areas requiring better disinfection practices.

 

5/30 SYNTHESIS AND ANTIOXIDANT ACTIVITY OF SOME NOVEL FUNCTIONALIZED N-SUBSTITUTED BENZIMIDAZOLE DERIVATIVES

Mohamed M. Said , Nagat Ghareb, *Pierre Hanna and **Adel A. El-Gendy

Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University, Egypt;

*Pharmaceutics Department, Faculty of Pharmacy, Suez Canal University, Egypt;

**Organic Chemistry Department, Faculty of Pharmacy, Misr International University, Egypt

Benzimidazole 5a-f were synthesized by ring opening reaction of oxirane 4. Reaction of acetohydrazides 9-11with cyclizing reagents gave 12a-b, 13a-b, 14a-b and 15a-b. thiosemicarbazides and semicarbazides 16-22 were converted to 23a-g. 24a-g. 25a-g. 26a-g and 27a-g. The antioxidant activities were tested in vitro using DPPH radical scavenging assay. Some of the tested compounds showed promising antioxidant activities.

 

6/30 SYNTHESIS AND ANTIOXIDANT ACTIVITY OF SOME BENZIMIDAZOLE AND INDOLE DERIVATIVES CONTAINING [1, 2, 4]TRIAZOLE RING.

Mohamed M. Said , Nagat Ghareb, *Pierre Hanna and **Adel A. El-Gendy

Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University, Egypt;

*Pharmaceutics Department, Faculty of Pharmacy, Suez Canal University, Egypt.

**Organic Chemistry Department, Faculty of Pharmacy, Misr International University, Egypt

The oxadiazoles 4a-c were converted to the corresponding 4-amino-5-((2-subsituted phenyl-1H-benzo[d]imidazol-1-yl) methyl)-4H-1, 2, 4-triazole-3-thiols 5a-c by hydrazinolysis. Cyclocondensation of 5a-c with 2-bromo-1-(naphthalen-1-yl)ethanone and ethyl orthoformate led to 6-(naphthalen-1-yl)-3-((2-phenyl-1H-benzo[d]imidazol-1-yl)methyl)-7H-[1,2,4]triazolo[3,4 b][1,3,4]thiadiazines 6a-c and 3-((2-subsitutedphenyl-1H-benzo[d]imidazol-1-yl)methyl)-[1,2,4]triazolo[3,4-b]-[1,3, 4]thiadiazoles 7a-b respectively. Condensation of 2-(2-(2-(4-methoxyphenyl)-1H-benzo[d]imidazol-1-yl) acetyl) hydrazinecarbothioamide 8 with hydrazine afforded 5-((2-(4-methoxyphenyl)-1H-benzo[d]imidazol-1-yl) methyl)-4H-1,2,4-triazole-3,4-diamine 9. Ring closure of oxadiazole 11 with an excess of hydrazine hydrate afforded 4-amino-5-(5-fluoro-1H-indol-2-yl)-4H-1, 2, 4-triazole-3-thiol 12 whose reaction with 2-bromo-1-(naphthalen-1-yl)ethanone and ethyl orthoformate in presence of DMF led to thiadiazine 13 and 3-(5-fluoro-1H-indol-2-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole 14 respectively. The antioxidant activities were tested in vitro using DPPH radical scavenging assay.

 


7/30 ERTHROCYTES SUPEROXIDE DISMUTASE ACTIVITY IN CHRONIC LIVER DISEASES

Badria Shamsan

Department of Biochemistry, Faculty of Medicine and Health Science, Sana'a University, Yemen

The liver plays a central role in many essential physiological processes and is particularly susceptible to reactive oxygen species. Superoxide dismutase (SOD) and catalase (CAT) are one of the protective mechanisms against the oxidative damage, both in the circulation and in erythrocytes. The activities of SOD, CAT and levels of Cu++ in the haemolysate and plasma of (123) patients with chronic liver diseases which were: 24 patients with hepatosplenomegaly (HSM), 20 patients with obstructive jaundice (Ob.Jn) due to extra or intra hepatic causes, 14 patients suffering from chronic hepatitis (Hv) due to B or C viruses without cirrhosis, 12 patients with liver cirrhosis (LC), which was due to either alcoholic or viral causes, 14 patients with liver malignant diseases (LM), (metastatic liver disease and hepatocellular carcinoma), 11 male patients with alcoholic liver disease (Al. LD), 7 patients with portal hypertension (P.Hy), 5 patients with recurrent gall stone (RGS) and 16 patients with miscellaneous liver diseases such as: (Wilson's disease, Budd-chari syndrome, Gilbert disease, Autoimune disease with primary billiary cirrhosis, Bechet's disease, Adison's disease, hepatic comma and chronic liver disease with unknown etiological cause.) 24 normal control subjects (whose age and sex were matched), were studied. The present study revealed a highly significant increase of hemolysate and plasma MDA in all the different liver diseased groups (p<0.01) and (p<0.05) respectively, than that of the control subjects, which was accompanied with a non significant increase in the erythrocyte and plasma SOD activities in all of the diseased groups, as compared to that of the control group by (HSM and Ob.J 14.39%, Hv 23.27%, LC 32.77%, ML 19.34%, P.Hy 6.12%, Al.LD 51.9%, MLD 22.15% and RGS 10.29%) and (HSM 23.24%, Ob.Jn 10%, Hv 15%, LC 7.88%, LM 16.42%, P.Hy 9.89%, Al.LD 2%, MLD 17.2%) for RBC-lysate and plasma respectively. The data also showed that CAT activities were found to be significantly increased in hemolysate of all the liver diseased groups, as compared to that of the control group (P<0.05) but a non significant increase of plasma-CAT in the liver diseased groups, (HSM 17.7%, Ob.Jn 30%, LC 3.2%, LM 5.8%, P.Hy 23.4%, Al.LD 23.1% and MLD 11.7%) as compared to that of the control group. In addition the study depicted a significant increase in erythrocyte Cu++ and plasma Cu++ levels by (P< 0.01) in the different liver diseased groups as compared to that of the control group. Our findings indicating that patients with chronic liver diseases have increased SOD and CAT enzymes activities with increase of oxidative stress accompanied with Cu++ accumulation .

8/30 ASSOCIATION BETWEEN CHRONIC H. ELICOBCTER PYLORI INFECTION AND CORONARY HEART DISEASE INCIDENCE IN SANA'A, YEMEN

Nabila Mohammed Mohammed and Dheya Abdul-Hafeed Sharaf Al-Danani.

Department of Medical Microbiology, Faculty of Medicine and Health Sciences. Sanaa University, Yemen

One hundred and forty eight patients with coronary heart disease (CHD), [myocardial infarction (MI) was the main picture of CHD in this study] were admitted to the intensive care unit (ICU) and medicine department of the three main hospitals (Al-Thawra general hospital, Al- Jumhori teaching hospital and Al- Kuwait university hospital.Out of the 148 patients, 115 were men while 33 were women. Their ages ranged between 40-65 years old. Also one hundred and forty eight apparently healthy control subjects, whose age and sex were matched. This study was conducted to determine the seroprevalence of H. pylori among cases and control groups, by serological survey. In addition to determine the association between CHD and chronic H. plori infection in Yemeni people who live in Sana'a. Finally to correlate the seroprevalence of H.pylori IgG antibodies among CHDpatients with some risk factors. The results obtained from this study that, 114(77%) of CHD patients were anti- H. pylori IgG positive (OR= 2.5; 95%CI= 1.46-4.2; PV= 0.0003) while 85(57.4%) of control subjects were anti-H.pylori IgG positive (OR= 0.4; 95%CI= 0.24-0.69; PV= 0.0003) and the highest seroprevalence of anti-H. pylori IgG antibodies was found in oldest age group (60-65yrs) (OR= 1.87; 95%CI= 1.02-3.2).This study also revealed a strong statistical association for the presence of chronic H. pylori infection in CHD patients, which suggest the increased risk for CHD. Eighty (70.2%) of CHD patients with anti- H. pylori IgG positive were cigarette smokers and 94 (82.5%) of them were chewing qat. From this study, it can be concluded that, first the seroprevalence of anti-H. pylori (IgG) antibodies among the CHD patients was 77% while it was 57.4% among the control subjects. Second, there was a strong association between chronic H. pylori infection and CHD in Sana'a Yemen. Third, the higher percentage of anti-H. pylori IgG antibodies in CHD patients was among the smokers and who chewing qat which considered as risk factors among them.

 

9/30 ERYTHROCYTES GLUTATHIONE LEVELS IN CHRONIC LIVER DISEASES

Badria Shamsan

Department of Biochemistry, Faculty of Medicine and Health Science, Sana'a University, Yemen

Liver is particularly susceptible to reactive oxygen species. Reduced glutathione (GSH) and its related enzymes (glutathione peroxidase GPx, glutathione-S-trasferase GST) are one of the protective mechanisms against the oxidative damage, both in the circulation and in erythrocytes. The levels of thiobarbituric reactive substances (TBARS), glutathione (GSH) and its transformation enzyme activities (GPX), (GR) and (GST) in the haemolysate and plasma of (143) patients with chronic liver diseases who were: 28 patients with hepatosplenomegaly (HSM), 24 patients with obstructive jaundice (Ob.Jn) due to extra or intra hepatic causes, 20 patients suffering from chronic hepatitis (Hv) due to B or C viruses without cirrhosis, 21 patients with liver cirrhosis (LC), which was due to either alcoholic or viral causes, 13 patients with liver malignant diseases (LM), (metastatic liver disease and hepatocellular carcinoma), 9 male patients with alcoholic liver disease (Al. LD), 7 patients with portal hypertension (P.Hy), 5 patients with recurrent gall stone (RGS), 16 patients with miscellaneous liver diseases (MLD) such as: (Wilson's disease, Budd-chari syndrome, Gilbert disease, Autoimune disease with primary billiary cirrhosis, Bechet's disease, Adison's disease, hepatic comma and chronic liver disease with unknown etiological cause.) and (24) normal control subjects (whose age and sex were matched), were evaluated. The present study revealed a highly significant increase of hemolysate and plasma MDA in all the different liver diseased groups (p<0.01) and (p<0.05) respectively, than that of the control subjects. The results also indicated that although, there were a high significant difference in hemolysate-GSH contents (p<0.05) of the most liver diseased groups than that of the control subjects, except for its mean in (P.hy) group which showed a slight decrease; plasma GSH levels showed a highly significant decreased in the liver diseased groups as compared to that of the control group (p<0.0l). The data showed there were an increase in the hemolysate-GR activities in all liver diseased groups by (LM 96%, LC 86%, 54% for Ob.Jn and HSM, 30% for Al.LD and P.Hy, MLD 28%, Hv. 22% and RGS 12%), than that of the control group but with nonsignificant difference. The study also depicted a nonsignificant increase in the activities of GPx and GST in all liver diseased groups by (LM 63.7%, LC 22.6%, HSM 11.6%, Al.LD 39%, P.Hy 2.7%, MLD 5.4%, Hv. 8.8%, but a slightly decreased in RGS by 2.3%) and (LM 21%, LC 18.5%, Ob.Jn 11.5%, HSM 11.3%, Al.LD 42.6%, P.Hy 13.7%, MLD 40%, Hv. 28.6% and RGS 17.6%) respectively, as compared to that of the control group. Our findings provide compelling evidence that patients with chronic liver diseases have increased glutathione and glutathione transformation enzymes activities with increase of oxidative stress.

10/30 CYTOTOXIC MARINE EXTRACTS

Farouk R. Melek,*Mohammed A. Selim, **Mohammed S. Beder, ***Ahmed M. Emara, Marwa H. Hassan

FROM

Department of Natural Compounds, National Research Center, Dokki, Giza, Egypt.

*Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Egypt.

**Central Administration for Protecting Nature, Egyptian Environmental Affair Agency.

***Hydrobiology Laboratory, National Institute of Oceanography and Fisheries Red Sea and Suez and Aqaba Gulfs Branch.

The methanolic extracts of 78 diverse marine organisms collected from the Red Sea, were screened for their cytotoxic activities. The results showed that among the tested extracts, 11 extracts exhibited lethality on brine shrimp. Additionally, 18 extracts exhibited variable toxicities against five human tumor cell lines in vitro. The potential effects were evaluated by determining the LC50 and LC90 for the brine lethal extracts and the IC50 for the extracts proved to be cytotoxic against human cell lines. The extracts of the soft coral Sarcophyton trocheliophorum and the sponge Latrunculia magnifica exhibited the highest brine shrimp lethality with LC50 values 20μg/ml and 21μg/ml, respectively. The most significant cytotoxic effects against HEPG-2 cell line were observed by the extracts of Latrunculia magnifica (0.13μg/ml), the echinoderms Actinopyga echinites (0.77μg/ml) and Holothuria nobilis (1.30μg/ml) together with the alga Caulerpa taxifolia (1.01μg/ml). The most potent cytotoxic activities against U-251 cell line were shown by the extracts of Latrunculia magnifica (0.70μg/ml), the echinoderm Holothuria polii (0.74μg/ml) and Sarcophyton trocheliophorum (1.14μg/ml). Extracts of Caulerpa taxifolia (1.07μg/ml) and C. racemosa (1.81μg/ml) exhibited marked activities against HELA cell line. The highest cytotoxic extracts against MCF-7 cell line were derived from Caulerpa racemosa (0.47μg/ml), Saragassum latifolium (0.47μg/ml) and Caulerpa taxifolia (0.54μg/ml). The extracts of the sponge Ianthella flabelliformis (9.26μg/ml) and Sarcophyton trocheliophorum (10.00μg/ml) were cytotoxic against H-460 cell line.

11/30 DESIGN AND EVALUATION OF INDOMETHACIN LOADED - EUDRAGIT FILMS PLASTICIZED WITH DIFFERENT PLASTICIZERS

Sherin A. El-Adawy and Dalia A. Attia

Pharmaceutics Department, Faculty of Pharmacy (girls), Al-Azhar University,

Nasr City, Cairo, Egypt

The objective of the present study was to evaluate the anti-inflammatory effect of Indomethacin loaded films prepared with series of acrylic resin films; (Eudragit L100, Eudragit S100, and Eudragit L100-55). The study of the in–vitro release of indomethacin from the prepared Eudragit films and the effect of adding oleic acid and diethyl phthalate as plasticizers in two different ratios (5% and 10%) for each plasticizer to each type of Eudragit was investigated. The effect of different temperatures on the release was studied, and the thermodynamic parameters of drug permeation were calculated. Also the anti-inflammatory effects of indomethacin in selected Eudragit films were determined in adult albino male rat, using paw edema method. The results suggested that the release of drug from the prepared films was directly proportional to the temperature. At 40oC, the release of indomethacin was higher than that at both 37oC, and 34oC. It was observed that 10% diethyl phthalate in Eudragit L100, Eudragit S100 and Eudragit L100-55 had the highest in-vitro release of the drug. So, they were chosen for clinical study of the anti-inflammatory effect of the drug in topical Eudragit films by measuring the mean percentage of inhibition in edema thickness in rats and it was compared to control group. Finally, from this study, it was possible to formulate transdermal indomethacin delivery system which can produce significant topical anti-inflammatory effect.

12/30 CHEMICAL AND BIOLOGICAL STUDY OF SOME ACTIVE CONSTITUENT FROM CHROZOPHORA OBLIQUA VAHL. ROOT

Taha S. El-Alfy*, Mona El-Tantawy**, Aly M. Fahmy***and Maie S. Khader**

*Dep. of Pharmacognosy, Faculty of Pharmacy, Cairo University,

**National Organization For Drug Control and Research (NODCAR),

***VACSERA- Egypt

Chrozophora obliqua Vahl roots growing in Egypt were investigated for their sulphur glycosides and polysaccharides contents. Seven isothiocynates were identified using GCand EI/MS technique .These compounds are 6- methylsulfonylhexyliso-thiocyanate {1} methyl sulphonyl propyl isothiocyanate {2},4- methane sulphinyl-butyl isothiocyanate (sulphoraphan) {3}Benzyl isothiocyanat (glucotropaeolin) {4} methyl sulphonyl heptyl isothiocyanate {5}5-benzyl sulfonyl-4-pentenyl isothiocyanate{6}, 9, 9 - dimethyl, 2, 5 decadienyl isothiocyanate{7}.These compounds are reported for the first time from Chrozophora species. The antitumor activity of the isolated isothiocyanates and ethyl alcohol extract was carried out using two cell lines; HCT116 and U251. Spectroscopic and chromatographic study of the polysaccharide content of Chrozophora obliqua Vahl. revealed the presence of two main monomeric sugars arabinose 76.7% and xylose 12.5% in addition to sulfate moiety. The antiviral and antitumor activity of the polysaccharides carried out showed a remarkable antiviral and anticancer activities against HSV-1 and VSV virus in HEPG2- and MCF7-P cell lines respectively.

 

13/30 STUDY OF THE CONSTITUENTS AND BIOLOGICAL EFFECT OF THE SEEDS PARKINSONIA ACULEATA L.

Taha S. M.El-Alfy*, Mona E. El Tantawy**, Amany A. Sleem*** Ghada F. Metwally**** and Marwa Hassan*∙

* Department of Pharamacognosy, Faculty of Pharmacy, Cairo University.

** Chairman of National Organization for Drug Control and Research, (NODCAR), Agouza, Giza

*** Department of Pharamacology, National Research Centre, Dokki, Giza.

**** Department of Tissue Culture, (NODCAR), Agouza, Giza.

*∙ Pharmaco Centre, (NODCAR), Agouza, Giza

A nearly complete analysis of the seeds of Egyptian Parkinsonia aculeata L. (Family Caesalpiniaceae) was performed in this study. The protein represented 23.5% in which glutamic acid, arginine and aspartic acid were the main amino acids. The major minerals in the seeds were calcium, magnesium and sulfur. The mucilage was found to be 9.01% and GC analysis showed the main sugars to be galactose and mannose in the molar ratio of 1:1.7. The alkaloid 4-hydroxy-13-methoxysparteine [1] was isolated, for the first time from the seeds, the structure was deduced by means of MS and NMR spectral analyses. Four gel formulations prepared from the mucilage were studied physicochemically showing F1 and F2 to possess reasonable rheological properties, favourable spreadability and extrudability characteristics and physically stable. The gel containing 1% mucilage (F2) had significantly enhanced wound healing compared to that containing 0.5% mucilage (F2).The raw mucilage exhibited good hypocholesterlemic and hypoglycemic activities.

14/30 DNA FINGERPRINTING, PROTEIN PROFILE AND ESTABLISHMENT OF TISSUE CULTURE CALLUS PROTOCOL OF CHROZOPHORA OBLIQUA VAHL.

Taha S. El-Alfy*, Mona El-Tantawy**, Sahar A.Tawab***and MaieS. Khader**

* Dep. of Pharmacognosy, Faculty of Pharmacy, Cairo University.

** National Organization for Drug Control and Research (NODCAR).

*** Department of Botany, Faculty of Women, Ain Shams University

An efficient and promising protocol for achievement and enhancement of calli production from seeds of Chrozophora obliqua Vahl, family Euphorbiaceae was established. The effect of different concentrations of 2, 4-dichlorophenoxy acetic acid (2, 4-D) and Kinetin in addition to MS- media on initiation of the callus production and the effect of the different growth regulators on callus mass production were investigated. The callus growth parameters were determined. Moreover the main active constituents of the plant were evaluated. In addition, the DNA fingerprinting of Chrozophora obliqua Vahl. via the (RAPD-PCR) the molecular genetic marker technique was also conducted. Protein electrophoresis was carried out to monitor the seed storage protein, expressed by the genes, by SDS-PAGE(PolyAcrylamide Gel Electrophoresis) technique.

15/30 SYNTHESIS AND MOLECULAR MODELING OF NOVEL 2-PYRIDONES AS POTENTIAL PIM-1 KINASE INHIBITORS

Hend M. El-Sehrawi and Magda M. F. Ismail

Pharmaceutical Chemistry Department, Faculty of Pharmacy (Girls),

Al-Azhar Universiy, Cairo, Egypt.

A novel series of 2-pyridones were synthesized through reaction of cyanoacetanilides, 1 with either acetylacetone or aromatic aldehydes and methylarylketones in one-pot-reaction forming novel series of 4,6-disubstituted-2-oxo-1,2-dihydropyridine-3-carbonitriles, 2-7. Moreover, one-pot-reaction of 1 with appropriate aldehydes, malononitrile/ethylcyanoacetate furnished the target compounds, 6-amino-1-aryl-4-phenyl/substitutedphenyl-2-oxo-1,2-dihydropyridin-3-carbonitrile derivatives 8-15. The pyridones, 9 and 10 were allowed to react with formamide to afford the desired 4-amino-7-oxo-5-phenyl-8-substitutedphenyl-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbontriles, 16 and 17. Docking studies of the newly synthesized compounds into the active site of Pim-1 kinase was carried out and showed that compounds 2, 10 and 15 possessed the highest binding affinity with minimal energy than the reference and thus could be used in designing potential inhibitors of Pim-1 Kinase.

 

16/30 A NEW 28-NOR PENTACYCLIC TRITERPENE AND STEROLS FROM GLEDITSIA SPECIES CULTIVATED IN EGYPT

Ehab A. Ragab, Ezzat A. M. Genady, and Usama Y. Shaheen

Pharmacognosy Department, Faculty of Pharmacy, Al-Azhar University,

Cairo, Egypt.

A new 28-nor pentacyclic triterpene (1), together with a known compound; β-sitosterol (2) were isolated from the fruits of Gleditsia caspia Desf and the known β-sitosterol glucoside (3) in addition to β-sitosterol (2) were isolated from the fruits of Gleditsia aquatica March. The structure of the new compound (1) was determined on the basis of spectroscopic methods including; 1H, 13C NMR, DEPT, COSY, HSQC, HMBC and EIMS experiments. The anti-inflammatory activity of the new compound, EtOAc and n-BuOH soluble fractions of Gleditsia aquatica was evaluated.

 

 

17/30 FORMULATION, IN-VITRO PERFORMANCE AND BIOAVAILABILITY STUDY OF FLOATING METRONIDAZOLE TABLETS

Alaa A. Kassem, Maha A. Marzouk and Dalia A. Attia

Pharmaceutics Department, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt.

The objective of this study is to develop a floatable drug delivery system for controlled delivery of metronidazole (MT) commonly used in eradication of Helicobacter pylori infection. MT tablets containing Carbopol 934P (CBP), carboxy methylcellulose (CMC) and methyl cellulose (MC) as polymers, in different drug to polymer ratios, prepared by direct compression technique are complied with the pharmacopoeial requirements for quality control testing. In-vitro release study was done for MT tablets. MT tablets with extended release results up to 6 hours were formlated into bilayer tablets using gas-generating layers. Stable and persistent buoyancy of MT bilayer tablets was achieved in the range of 3-60 minutes. The investigated MT tablets were subjected to an in-vivo study by administration orally to human volunteers, and the pharmacokinetic parameters were calculated. Also the relative bioavailability of the prepared tablets compared to the commercial product, was estimated. MT tablets containing CMC in drug: polymer ratio of 1:1 was found to be the best formula, as it showed the highest area under the curve, AUC 0-∞ (μg.hr/ml), mean residence time, MRT(hr) and relative bioavailability (%RB) while it showed the shortest tmax (hr). The developed delivery system of MT had increased the efficacy of the therapy for Helicobacter pylori associated ulcers as dose can be reduced and incomplete drug absorption can be avoided, in addition to the improvement of patient compliance.

 

18/30 POSSIBLE PROTECTION AGAINST ENDOTOXEMIA-INDUCED LIVER DYSFUNCTION IN RATS BY THYMOQUINONE SUPPLEMENTATION

Gouda K Helal and *Hossam M Ashour

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Egypt.

*Department ofMicrobiology and Immunology, Faculty of Pharmacy, Cairo University, Egypt.

Endotoxemia caused by lipopolysaccharide (LPS) resulted in an inflammatory condition contributing to multiple organ failure including hepatotoxicity. This study was carried out to investigate if thymoquinone (TQ), the main constituent of Nigella sativa seeds, can act against LPS-induced hepatotoxicity. The obtained data revealed that LPS markedly depleted liver reduced glutathione (GSH) and significantly increased the level of malondialdehyde (MDA) and the activity of caspase-3 enzyme in the liver. Serum tumour necrosis factor-alpha (TNF-α) and bilirubin levels and the activities of alkaline phosphatase (ALP) and gamma-glutamyl transferase (γ-GT) enzymes were markedly increased in LPS-treated rats. TQ supplementation resulted in normalization of liver GSH and marked decreases in the levels of liver MDA and caspase-3 activity along with reductions of serum TNF-α, serum total bilirubin and the activities of ALP and γ-GT enzymes. Moreover, histopathological examination revealed that TQ administration improved LPS-induced pathological abnormalities in liver tissues. The current study suggests that TQ reduced acute endoxemia-induced liver dysfunction at least in part by anti-inflammatory, antiapoptotic and antioxidant mechanisms.

19/30 PREPARATION AND IN VITRO EVALUATION OF KETOCONAZOLE-LOADED EUDRAGIT MICROSPHERES

Dalia A. Attia

Pharmaceutics department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt

The utility of two linear polymethacrylates (Eudragit RS and RL) to encapsulate and control the release of ketoconazole, via microspheres, was investigated. Microspheres were prepared by solvent evaporation method using acetone/liquid paraffin system. The influence of formulation factors (polymer: drug ratio, type of polymer, ratio of the combination of polymers) on particle size, encapsulation efficiency, flow property, bulk and tap densities and in vitro release characteristics of the microspheres were investigated. The yield of preparations and the encapsulation efficiencies were high for most formulations. Microencapsulation technique improves the flow properties of ketoconazole as declared by Hausner ratio and compressibility percent. Mean particle size changed by changing the polymer: drug ratio. As general rule, increasing the coat to core ratio causes increase the sustaining effect induced by all the polymers used i.e. the concentration of the polymer correlate negatively with the in vitro release of the ketoconazole. Although ketoconazole release rates from Eudragit RS microspheres were very slow and incomplete for most formulations, they were fast from Eudragit RL microspheres. When Eudragit RS was blended with Eudragit RLin the microsphere formulations, release rates were controlled over 24 hr and achieved a release profile probably for peroral administration.

Scroll to top