Synthesis and pharmacological evaluation of 8-substituted phenyl xanthines for asthma therapy
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1
Banasthali University, Pharmacy, India
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2
Panjab University, Chandigarh, University Institute of Pharmaceutical Sciences, India
Xanthines belongs to an important class of drugs used in the treatment of asthma and have been considered to be the most effective prophylactic agents for the control of symptoms of chronic asthma. Currently, adenosine receptor antagonists (AdOR) are reported to be novel therapeutic antiasthmatic agents. Development of receptor target inhibition is a novel approach in current drug design scenario. In the last few year’s xanthines have received considerable attention as molecular targets for the development of antiasthmatic agents. Several positions of xanthine skeleton with different substituent have been explored to obtain a variety of potent derivatives.Present investigation has been made to design potent selective xanthine derivatives, synthesize and screen them in vitro (adenosine antagonism) and in vivo (BAL analysis) for antiasthmatic activity. To observe the effects of morpholino substituted group, a new series of 8-(substituted-phenyl) xanthines has been synthesized and compounds were evaluated for their affinity for A1 and A2A adenosine receptors (AR) using radioligand-binding assays. The synthesized xanthine derivatives exhibited varying degrees of affinity and selectivity towards A1 and A2A receptor subtypes. As a part of research study, we further examined the dynamic changes in cellular profile of bronchoalveolar lavage (BAL) fluid after lipopolysaccharide (LPS) challenge in the male wistar rats of synthesized xanthine derivatives.In general, the newly synthesized compounds displayed significant antiasthmatic activity. The outcome of the current work is the generation of an important pool of new xanthine derivatives.
References
1. Bansal, R.; Kumar, G.; Gandhi, D.; Yadav, R.; Young, L. C.; Harvey, A. L. Synthesis of 8-(cyclopentyloxy)phenyl substituted xanthine derivatives as adenosine A2A ligands. Arzneim.-Forsch. 2010, 60(3), 131-136.
2. Zabeer, A.; Bhagat, A.; Gupta, O. P.; Singh, G. D.; Youssouf, M. S.; Dhar, K. L.; Suri, O. P.; Suri, K. A.; Satti, N. K.; Gupta, B. D.; Qazi, G. N. Synthesis and bronchodilatory activity of new quinazoline derivative. Eur. J. Med. Chem. 2006, 41, 429-434.
3. Ali, S.; Mustafa, S. J.; Metzger, W. J. Release of adenosine in bronchoalveolar lavage fluid following allergen bronchial provocation in allergic rabbits. J. Pharmacol. Exp. Ther. 1996, 96, 639-644.
Keywords:
adenosine receptors,
Bronchoalveolar Lavage Fluid,
Xanthine derivatives,
Lipopolysaccharides,
G-protein coupled receptor (GPCR)
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune receptors and signaling
Citation:
Yadav
R,
Yadav
D,
Bansal
R and
Kuhad
A
(2013). Synthesis and pharmacological evaluation of 8-substituted phenyl xanthines for asthma therapy.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00645
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Received:
13 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Rakesh Yadav, Banasthali University, Pharmacy, Banasthali, 304022, India, rakesh_pu@yahoo.co.in