Materials & methods: Fifty-one novel 12N-substituted matrinic acid derivatives were synthesized and evaluated for their anti-coxsackievirus B3 activities.
Results: Structure-activity relationship studies revealed that the 11-side chain could be determinant for the selectivity index by adjusting overall lipophilicity, and 11-butane was the best one for both potency and druggability. The optimized 35d showed the broad-spectrum anti-coxsackieviruse effects, an excellent pharmacokinetics and a good safety profile. More importantly, it displayed a potential effect for the pleconaril-resistant coxsackievirus B3 as well. Its mode of action is targeting on the viral transcription and translation stage, a different mechanism from that of pleconaril.
Conclusion: Thus, we considered that 35d is a promising anti-enteroviral candidate for the treatment of various diseases infected with coxsackieviruses.
Keywords: coxsackieviruse; druggability; matrinane; matrinic acid; structure–activity relationship.