Synthesis and QSAR study of the anticancer activity of some novel indane carbocyclic nucleosides

• Type: Article in International Scientific Journal
• Date: 2003

Authors

Yao, SW (Author) Other; Lopes, VHC (Author) Other; Fernandez, F (Author) Other; Garcia Mera, X (Author) Other; Morales, M (Author) Other; Rodriguez Borges, JE (Author) FCUP; Cordeiro, MNDS (Author) FCUP

Journal

Title: Bioorganic and Medicinal Chemistry

Vol. 11

Pages: 4999-5006

ISSN: 0968-0896

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 74 Citations

Scopus - 81 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-000-EEJ

DOI: 10.1016/j.bmc.2003.09.005

Abstract (EN): A set of 14 indane carbocyclic nucleosides were synthesized and experimentally assayed for their inhibitory effects in the proliferation of murine leukemia (L1210/0) and human T-lymphocyte (Molt4/C8, CEM/0) cells. The compounds have promising inhibitory activity judging from the IC50 values obtained for all these cellular lines. Multiple linear regression analysis was then applied to build up consistent QSAR models based on quantum mechanics-derived molecular descriptors. The derived models reproduce well the experimental data of both three cells (r(2) greater than or equal to 0.90), display a good predictive power (r(CV)(2) greater than or equal to 0.86) and are, above all, easily interpretable. They show that frontier-orbital energies and hydrophobicity are mainly responsible for the activity of the synthesized compounds and also, suggest similar mechanisms of action. The final QSAR-models involve only two descriptors: the lowest unoccupied molecular orbital energy and the solvent accessible-hydrophobic surface area, but describe a sound correlation between predicted and experimental activity data (r(2) = 0.931, r(2) = 0.936 and r(2) = 0.931 for the cells L1210/0, Molt4/C8 and CEM/0, respectively).

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8