International Journal of Pharmacy and Pharmacology

International Journal of Pharmacy and Pharmacology ISSN: 2326-7267 Vol. 4 (1), pp. 001-009, January, 2013. © International Scholars Journals

Full Length Research Paper

Design, Synthesis and biological evaluation of novel acridine-polyamine conjugates against prostate cancer

Hildebert B. Maurice^1*, Rodger Phillips² and Nazira Karodia³

¹School of Pharmacy, St. John’s University of Tanzania, P.O. Box 47 Dodoma Tanzania.

²Yorkshire Cancer Research, University of Bradford, West Yorkshire, BD7 1DP, UK.

³School of Chemistry and Forensic Sciences, University of Bradford, West Yorkshire, BD7 1DP, UK.

Accepted 24 May, 2012

Abstract

Prostate cancer is the most common cause of cancer death in men, aged 85 and over. Androgen receptor, a single polypeptide with three functional domains is very important during initiation and progression of the disease. In this study, a DNA intercalating agent, acridine is linked to the testosterone via a polyamine linker to obtain a compound with trifunctional characteristics, where the acridine intercalates the DNA, the polyamine linker binds the phosphoryl groups of the DNA backbone and the testosterone moiety binds into the AR ligand binding domain, with which its DNA binding domain is bound already to the DNA. This trifunctional compound and related derivatives have been synthesized and tested against androgen dependent- and androgen independent- prostate cancer cell lines and they have demonstrated to be cytotoxic at the micromolar concentrations.

Key words: Polyamines, Testosterone, Prostate cancer, Acridine, Synthesis.

International Journal of Pharmacy and Pharmacology ISSN: 2326-7267 Vol. 4 (1), pp. 001-004, January, 2012. © International Scholars Journals

Review

Antiplasmodial activity of various parts ofPhyllanthus niruri according to its geographical distribution

P.  Njomnang Soh^{1, 2}, J. T. Banzouzi^{3, 4}, H. Mangombo⁵, M. Lusakibanza⁵, F. O. Bulubulu⁶, L. Tona⁵, A. N. Diamuini⁶, S. N. Luyindula⁶ and Françoise Benoit-Vical^{1, 2}*

¹Parasitology-Mycology Department, Rangueil Hospital University, TSA 50032, 31059 Toulouse 9, France & University of Toulouse, 31059 Toulouse Cedex 9, France.

²CNRS ; LCC UPR8241; 205, route de Narbonne, F-31077 Toulouse, France AND University of Toulouse ; UPS, LCC; F-31077 Toulouse, France.

³ICSN-CNRS UPR2301, 91198 Gif-sur-Yvette cedex, France.

⁴CERMA, Médecins d’Afrique, BP 45, Brazzaville, Congo.

⁵Pharmacology Laboratory, University of Kinshasa, RD Congo.

⁶International Atomic Energy Agency (IAEA), BP 868. Kinshasa XI, RD Congo.

Accepted 15 October, 2012

Abstract

Extracts of Phyllanthus niruri L., collected from three different areas in the Congo (Kisantu, Kimwenza and University of Kinshasa), used for malaria treatment were tested in vitro in order to evaluate their antiplasmodial properties. Whereas the whole plant is traditionally used, aqueous extracts of the various parts of the P. niruri plant (stems, leaves and roots) tested on the chloroquine- resistant strain FcM29- Cameroon showed that only the leaves and the stems presented real in vitro antiplasmodial activity without any cytotoxicity. This information is particularly important because the leaves are affordable and their use is less damaging to plant stocks.

Key words: Ethno-pharmacology, Plasmodium falciparum, harvest areas, parts of plant.

International Journal of Pharmacy and Pharmacology Vol. 1 (3) pp. 034-040, December, 2012. © International Scholars Journals

Full Length Research Paper

Synthesis, structure and analgesic activity of 1-(2-cyanoethyl)- 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid hydroxy-alkylamides and their derivatives

Igor V. Ukrainets¹*, Olga V. Gorokhova¹, Xeniya V. Andreeva¹ and Galina Sim²

¹Department of Pharmaceutical Chemistry, National University of Pharmacy, Kharkiv 61002, Ukraine.

²Department of Pharmaceutical Chemistry, Far Eastern State Medical University, Khabarovsk 680000, Russia.

*Corresponding author. E-mail: [email protected] . Tel: +38-057-7098643.

Received 15 October, 2012; Accepted 10 December 2012

Abstract

The simple methods for obtaining have been suggested and the synthesis of new hydroxyalkylamides of 1-(2-cyanoethyl)-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid and their derivatives has been carried out by alcoholic hydroxyl. The peculiarities of the spatial structure of the given group of substances have been considered by an example of 3-isopropoxypropylamide. The research results of the analgesic activity of all the compounds synthesized are given; they confirm the expediency of searching new painkillers among quinoline-3-carboxamides. According to the results of pharmacological tests for in-depth study recommended (3-chloropropyl)-amide of 1-(2-cyanoethyl)-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid.

Key words: 3-aminopropanenitrile, 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbox-amides, triethyl methanetricarboxylate, analgesia, pain syndrome.

International Journal of Pharmacy and Pharmacology Vol. 3 (12) pp. 001-007, December, 2012. © International Scholars Journals

Full Length Research Paper

Halogen substitution anilides of 7-hydroxy-5-oxo-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-6-carboxylic acid as an attempt of optimization of quinolone diuretics by “me-too” method

Igor V. Ukrainets¹*, Igor N. Chernenok¹, Nikolai Yu Golik² and Vera N. Kravchenko³

¹Department of Pharmaceutical Chemistry, National University of Pharmacy, Kharkiv 61002, Ukraine.

² Department of Analytical Chemistry, National University of Pharmacy, Kharkiv 61002, Ukraine.

³ Department of Biology, Physiology and Human Anatomy, National University of Pharmacy, Kharkiv 61002, Ukraine.

 *Corresponding author. E-mail: [email protected]

Received 28 August, 2012; Accepted 19 November

Abstract

Using the principles of creating "me-too-drugs" halogen substitution anilides of 7-hydroxy-5-oxo-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-6-carboxylic acid have been synthesized as potential diuretics. According to the results of biological trials, the substances exceeding the diuretic effect of hydrochlorothiazide in sufficiently less dose have been revealed. It has been shown that like pyrroloquinolines, which were previously studied, 7-hydroxy-5-oxo-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-6-carboxamides can also be the base for new highly effective diuretics and are worthy of further research.

Key words: Amidation, anilides, 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamides, diuretics, "me-too".

International Journal of Pharmacy and Pharmacology Vol. 3 (12) pp. 025-028, December, 2012. © International Scholars Journals

Full Length Research Paper

VKORC1 haplotype diversity in the admixed Omani population: Significant presence of atypical haplotypes

Pathare A. V.¹*, Alzadjali S.¹, Misquith R.¹, Alkindi S.², Sahaya P.³, Paldi A.,⁴ and Krishnamoorthy R.³

¹Department of Hematology, Sultan Qaboos University Hospital, Muscat, Oman.

²College of Medicine and Health Sciences, Muscat, Oman.

³INSERM, UMR_S 665, Inserm/Université Paris Diderot, Paris, France.

⁴GENETHON, 1bis rue de l'Internationale, BP60, 91002 Evry, France.

*Corresponding author. E-mail: [email protected]

Received 01 October, 2012; Accepted 09 November, 2012

Abstract

There are significant differences in the performances of dosing algorithms between Caucasians, African Americans and Oriental populations owing to differences in the prevalence of genetic polymorphisms in enzymes involved in the pharmacokinetic and pharmacodynamic pathway, although other non-genetic factors do also contribute. The purpose of this work was to assess the vitamin K-epoxide reductase complex unit 1 (VKORC1) haplotypes in the Omani population for predicting specificity of warfarin dose response. We studied the pattern of five single nucleotide polymorphisms (SNPs) (rs 9923231; rs 9934438; rs 2884737; rs 17708472 and rs 7294) that define the VKORC1 haplotypes in healthy adult Omani subjects using a PCR-based targeted genomic DNA sequencing. The observed frequencies for VKORC1*1, *2,*3,*4 haplotypes were 0.08, 0.28, 0.29, 0.14 respectively. Four different novel haplotypes were found, two of which were present at a frequency above 3% in the Omani subjects. This is the first study to establish the VKORC1 haplotypes in Omanis. The predicted prevalence of warfarin sensitive VKORC1*2 haplotype was 27.8%, whereas it was 29.4 and 14.4% respectively for the haplotypes *3 and *4. The significant presence of VKORC1*1 haplotype (8%) in Omanis, (otherwise quite rare in Caucasians and Asians) can be traced back to their ancestral African admixture.

Key words: Pharmacogenetics, VKORC1, Omani, allele, haplotype.

International Journal of Pharmacy and Pharmacology ISSN: 2326-7267 Vol. 3 (12), pp. 001-006, December, 2012. © International Scholars Journals

Full Length Research Paper

Comparative effectiveness of Glycyrrhiza glabra vs. omeprazole and misoprostol for the treatment of aspirin-induced gastric ulcers

Mesut Sancar¹, Thaer Hantash¹, Betul Okuyan¹, Sule Apikoglu-Rabus¹, Zeynep Cirakli², Mine G. Gulluoglu³ and Fikret Vehbi Izzettin¹*

¹Clinical Pharmacy Department, Faculty of Pharmacy, Marmara University, Istanbul, Turkey.

²Biochemistry Department, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey.

³Pathology Department, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Accepted 25 August, 2012

Abstract

The aim of the study was to evaluate the comparative effectiveness of Glycyrrhiza glabra (liquorice) root decoction vs. omeprazole and misoprostol for the treatment of aspirin-induced gastric ulcers in rats. Animals were randomly assigned first to the “prophylaxis” and “treatment” groups and then to the test and the control groups. Liquorice decoction (25 ml/kg; i.g.); omeprazole (2.3 mg/kg; i.p.) and misoprostol (50 g/kg; i.g.) were administered for 3 consecutive days 30 min before aspirin (200 mg/kg, i.g.) administration, in the prophylaxis group. In the treatment group, aspirin (200 mg/kg, i.g.) was administered for 3 consecutive days, and then other drugs were administered at the same doses as the prophylaxis group daily for 4 weeks. According to histopathologic evaluation, misoprostol showed significant protection; however, liquorice decoction and omeprazole failed to protect. In the treatment group histopathological examinations showed no significant difference among liquorice decoction, misoprostol and omeprazole regarding aspirin-induced ulcer treatment; ulcers in all treatment groups were completely cured. The results of this study suggest that Glycyrrhiza glabra can be used for the treatment of NSAID-induced ulcers as an inexpensive alternative to misoprostol and omeprazole.

Key words: Aspirin, liquorice, misoprostol, nonsteroidal antiinflammatory drugs induced ulcers, omeprazole.