Cytisine is a natural alkaloid used in European countries as a smoking cessation drug due to its affinity towards the a4�2 nAChr. However, cytisine shows low bioavailability with serious side effects. Designing cytisine analogs with a higher affinity towards the receptor would reduce the dose needed to suppress the dopaminergic response and the toxic side effects of cytisine. Our approach involves the use of molecular docking  and QSAR studies to develop cytisine analogs that express a higher affinity for nAChr a4�2 than commercially available drugs. OpenEye� was used to create a virtual library of cytisine analogs and predict their interaction with the a4�2 nAChr. Several cytisine analogs with higher affinity than varenicline were synthesized. Binding affinity (Ki) values were used to prepare a QSAR analysis and predict the Ki values for the already synthesized compounds which ranged between 44-3236 nM. Synthesis of cytisine analogs and the in silico studies will be presented.

In silico study approach for the synthesis of cytisine analogs targeting the α<sub>4</sub>β<sub>2</sub> nAChr

244th National Meeting (2012)

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In silico study approach for the synthesis of cytisine analogs targeting the α4β2 nAChr

In silico study approach for the synthesis of cytisine analogs targeting the α₄β₂ nAChr