2D-QSAR and CoMFA Models for Antitubercular Activity of Scalarane-Type Sesterterpenes

A series of scalarane sesterterpenes were prepared using heteronemin (1) as a primary precursor. Combined with the scalarane derivatives obtained from natural sources, a total of 22 antitubercular scalaranes were used to build QSAR models based in the 2D-QSAR and CoMFA approaches. Both models indicated the influences of substitutions in the vicinity of C-12 and C-16 of the scalaranes. A 2D-QSAR model suggested the necessity of hydrophilic functionalities on the peripherals with hydrophobic cores, and the lowering steric repulsion to improve the potential energy. This was complemented by the pictorial CoMFA model, which indicated the importance of the positive electrostatic with shortened steric extension crowning over C-12 and the lengthy negative functionalities extended from C-16.

Automated summary

A series of scalarane sesterterpenes were synthesized using heteronemin (1) as the primary precursor. QSAR models based on 2D-QSAR and CoMFA approaches were built using a total of 22 antitubercular scalaranes obtained from natural sources and synthesis. The models indicated the significance of substitutions near C-12 and C-16 of the scalaranes.