Drug Design and Analysis In Silico of Sapelenin G, an Acyclic Triterpenoid as Potential Anti-Inflammatory

Diverse non-steriodal anti-inflammatory drugs and COX-2 inhibitors are a class of drugs which selectively inhibit COX-2, provide relief from pain and inflammation. 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 focus on the products originating from natural products that could offer better relief from inflammation 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 inflammation, pain and fever). The present study is undertaken to analyse the docking efficacy 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 finding suggests that sapelenin G is a better ligand than aspirin. It satisfies Lipinski Rule of 5. The PASS (Prediction of Activity Spectra for Substances) prediction results show that Sapelenin G has an anti-inflammatory 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 addition. A skin sensitization evaluation reveals that the compound has no skin sensitization alert identified, moreover, Kroes Threshold of Toxicological Concern (TTC) decision tree reveals that the Substance would not be expected to be a safety concern