Properties physicochemical involved in the coupling of thirty bicyclo derivatives with TrkA kinase and K‐Ras protein

Abstract Several bicyclo derivatives have been developed with biological activity against cancer; however, the interaction with some biomolecules involved in cancer growth is not clear. Analyzing these data, the aim of this study was to determine the interaction of thirty bicyclo derivatives ( 1 ‐ 30 ) with TrkA and K‐Ras using 4pmm and 4nmm proteins as theoretical tools. Besides, some drugs, such as selitrectinib, entrectinib, adagrasib, and sotarazib, were used as controls in the DockingServer program. The results displayed different numbers of amino acid residues involved in the interaction of bicyclo derivatives with either 4pmm or 4nmm protein surfaces compared to the controls. Other data showed that inhibition constants ( K i ) for compound 2 were in a similar manner to entrectinib; in addition, K i for compounds 2 and 10 was lower compared with selitrectinib and compounds 2 – 14 and 16 – 30 . Besides, other data indicate that K i for compounds 1 and 15 was lower compared with adagrasib, sotarazib, 1 , 10 , 15 , and 15 compounds, 1 , 2 – 14 , and 16 – 30 . In conclusion, all these data suggest that bicyclo derivatives 1 , 10 could act as TrkA inhibitors, and 1 and 15 may inhibit the biological activity of TrkA; this phenomenon could be translated as a good therapeutic alternative for treating cancer.