Abstract—Previous studies worked on the evaluation a few alkylxanthine derivatives synthesized from theobromine, exhibiting micromolar activities of the compounds against histamine in vitro. The structure-activity relationships study showed that the elongation of alkyl group at N
1 of xanthine ring increased the tracheospasmolytic activity. This result opened the opportunity for alkylxanthine to be developed as antihistamine. Presently, we elucidate the mechanism of N
1-alkylxanthine derivatives as antihistamine at a molecular level using pharmacophore modeling. The pharmacophore model was generated from a series of Histamine-H1 antagonists employing hydrogen bond acceptor (HBA), hydrogen bond donor (HBD) and two hydrophobic features and used as a search queries to map the N
1-alkylxanthine derivatives as Histamine-H1 antagonist. The results showed that all the designed ligands can adopt the pharmacophore features model providing the insight understanding about the opportunities of the N
1-alkylxanthine as Histamine-H1 antagonists.
Index Terms—Histamine, N
1-alkylxanthine, pharmacophore, antagonist.
Maywan Hariono is with Universiti Sains Malaysia, Malaysia (e-mail:maywan_har@yahoo.com, mh11_pha081@student.usm.my).
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Cite: Maywan Hariono and Habibah A. Wahab, "Pharmacophore Modeling of N1-alkyltheobromine as Histamine-H1 Receptor Antagonist," International Journal of Modeling and Optimization vol. 5, no. 2, pp. 98-103, 2015.