Journal
JOURNAL OF INCLUSION PHENOMENA AND MACROCYCLIC CHEMISTRY
Volume 90, Issue 1-2, Pages 157-169Publisher
SPRINGER
DOI: 10.1007/s10847-017-0773-x
Keywords
Calixarene; Inclusion complex; Bioavailability; Tyrosine kinases; Interaction energy
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Funding
- Science and Engineering Research Board (SERB)
- DST INSPIRE Fellowship [IF150167]
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Herein, an in-silico attempt was made to improve the pharmacological profile of second generation tyrosine kinase inhibitors (TKI's) viz. dasatinib, lapatinib and nilotinib by forming their host-guest inclusion complexes with calixarene. We have investigated the energetics and binding behaviour of TKI's with upper rim functionalised calix[n]arenes (n = 4,5,6 and 8) via appended groups (R=SO3H, tert-Butyl, iso-Propyl, COOH, C2H5OH, and C2H5NH2). For this, multilevel molecular docking approach with shape based fitting algorithms (Patchdock/Firedock and HexServer) followed by semiemperical PM3 calculations were employed to generate structural mode of complexes. Further, based on interaction energies and their structural integrity (dynamics behaviour), we concluded that the proposed drug carrier (host) for nilotinib (C2H5SO3H-calix[4]arene, and isopropyl/C2H5NH2-calix[8]arene), dasatinib (C2H5SO3H-calix[5]arene, C2H5COOH-calix[6]arene, tert-butyl-calix[6]arene) and lapatinib (C2H5SO3H/C2H5COOH-calix[6]arene and C2H5COOH-calix[8]arene) have the greater capability to form optimal complexes.
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