International Journal of Clinical Pharmacology & Toxicology, 2013 © 66 Ngabireng Marie. Claude, et al., (2013) Drug Design and Analysis In Silico Of Sapelenin G, An Acyclic Triterpenoid as Potential Anti-Inflammatory. Int J Clin Pharmacol Toxicol. 2(4), 66-72. International Journal of Clinical Pharmacology & Toxicology (IJCPT) ISSN 2167-910X Drug Design and Analysis In Silico of Sapelenin G, an Acyclic Triterpenoid as Potential Anti-Inlammatory Reserch Article Ngabireng Marie. Claude 1* , Menye Cyrille 2 , Kouam F.Simeon 3 , Ntede N .Hyppolite 4 , Tagoudjeu Jacques 1 , Awono Onana 1 1 National Advanced School of Engineering/Department of Mathematics and Physical Science, University of Yaounde I, Yaounde, Cameroon 2 Faculty of sciences/Department of Physics, University of Yaounde I, Yaounde, Cameroon. 3 Higher Teachers’ Training College/Department of Chemistry, University of Yaounde I, Yaounde, Cameroon. 4 National Advanced School of Engineering/Department of Mechanics and materials, University of Yaounde I,Yaounde, Cameroon. *Corresponding Author: Ngabireng Marie. Claude National Advanced School of Engineering/Department of Mathemat- ics and Physical Science, University of Yaounde I, Cameroon. E-mail: cngabire@yahoo.fr Received: June 06, 2013 Accepted: June 24, 2013 Published: June 27, 2013 Citation: Ngabireng Marie. Claude, et al., (2013) Drug Design and Anal- ysis In Silico Of Sapelenin G, An Acyclic Triterpenoid as Potential Anti- Inlammatory. Int J Clin Pharmacol Toxicol. 2(4), 66-72. Copyright: Ngabireng Marie. Claude © 2013. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. Introduction Sapelenin G, an acyclic triterpenoid, known under its UIPAC name as (10E, 14E, 18E)-2 ,6,10,15,19,23-hexamethyltetracosa- 10,14,18-triene-2,3,6,7,22,23-hexol (ig.1b) is a molecule extracted from a sapele tree scientiically known as Entadrophragma cylin- dricum[1]. It has been reported that triterpenes possess many use- ful properties among which anti-inlammatory [1,2]. This activity is manifested by their interaction with a number of targets [3]; including nitric oxide synthase (iNOS), nuclear factor-kB (NF- kB), heme oxygenase (HO) and cyclooxygenase (COX). The latest, also known as prostaglandin H Synthase (PGH syn- thase /PGHS/PHS) is a prominent and well-studied protein which catalyzes the conversion of arachidonic acid to prostaglan- din H2 (PGH2), the committed step in prostaglandin (PG) bio- synthesis. There are two isoforms of this enzyme: cyclooxygenase 1 (COX1) and cyclooxygenase 2 (COX2). COX1 are responsible for the maintenance and the protection of the gastrointestinal tract, COX2 is responsible for inlammation and pain [4]. The existing non-steroidal and anti-inlammatory drugs (NSAIDs) differ in their relative speciicities for COX-1 and COX-2; while aspirin is equipotent at inhibiting COX-2 and COX-1 enzymes in vitro [5]. The irst crystal structure of human cyclooxygenase-2, in the presence of selective inhibitor, is similar to that of cyclooxyge- nase-1; COX-1 and COX-2 are homodimers. The structure of NSAID binding site is also well conserved, although there are dif- ferences in its overall size. COX-1 and COX-2 are both targets of nonselective nonsteroidal anti-inlammatory drugs including aspi- rin and ibuprofen, while COX-2 activity is selectively blocked by COX-2 inhibitors called coxibs (e.g.,celecocib). Aspirin is a unique inhibitor that causes a time-dependent, covalent inhibition. In this study, we are reporting probable binding mechanism of sa- pelenin G with COX by molecular docking. This molecule shows a good binding to COX than aspirin and has drug-like properties. Abstract Diverse non-steriodal anti-inlammatory drugs and COX-2 inhibitors are a class of drugs which selectively inhibit COX-2, provide relief from pain and inlammation. However, they lack anti-thrombotic activity and hence lead to cardiovascular and renal liabilities apart from gastrointestinal irritation. To ameliorate this situation, research can be foccuss on the products originating from natural products that could offer better relief from inlammation than the currently used commercial drugs. Aspirin blocks the cyclooxygenase enzyme (COX 1, 2) which is involved in the ring closure and the addition of O2 to arachidonic acid, converting it to prostaglandins (which induce inlammation, pain and fever). The present study is undertaken to analyse the docking eficacy of aspirin with the target molecule (2AW1), to assess the best ligand for inhibiting COX and to analyze the docking program by Arguslab. Substituting aspirin ligand by sapelenin G, the inding sug- gests that sapelenin G is a better ligand than aspirin. It satisies Lipinski Rule of 5. The PASS (Prediction of Activity Spectra for Substances) prediction results show that Sapelenin G has an anti-inlammatory activity. Toxicity estimations of Sapelenin G using Toxtree on humans and based on the Cramer rules, Verhaar, Structural Alerts for Reactivity in Toxtree (START) biodegradability, eye irritation/corrosion and skin irritation/corrosion fell into class 3, 5, 1, 2 and 1, respectively. Application of the Benigni-Bossa method showed that this compound is negative for genotoxic carcinogenicity and negative for non-genotoxic carcinogenicity. The cytochrome P-450 mediated drug metabolism is negative for Sapelenin G only in SMARTCyp.Rank2.sites of metabolism, and it fell into unreactive group of compounds by Michael ad- dition. A skin sensitization evaluation reveals that the compound has no skin sensitization alert identiied, moreover, Kroes Threshold of Toxicological Concern (TTC) decision tree reveals that the Substance would not be expected to be a safety concern. Keywords: sapelenin G, cyclooxygenase, docking, anti-inlammatory activity.