Bcakground: In the present study we have explored the utility of QSAR modelling, in silico ADMET, docking, chemical semi-synthesis and in vitro evaluation studies for the identification of active camptothecin (CPT) derivatives against cancer targeting human liver (HepG2) and lung (A549) cancer cell lines.
METHODS:Two QSAR models were developed as screenings tools using multiple linear regression (MLR) method followed by ADMET and docking studies. The regression coefficient (r2) and cross-validation regression coefficients (rCV2T) of the QSAR model for HepG2 cell line was 0.95 and 0.90 respectively, and for A549 cell line it was 0.93 and 0.81, respectively.
RESULTS:In silico studies show that CPT derivatives (CPT-1 and CPT-6) possess drug-like properties. Docking performed on DNA Topoisomerase-I, showed significant binding affinity. Finally, predicted active derivatives were chemically semi synthesized, spectroscopically characterized and evaluated in-vitro for cytotoxic/anticancer activity against HepG2 and A549 cell lines.
CONCLUSION:The experimental results agreed with the predicted results. These findings may be of immense importance in the anticancer drug development from an inexpensive and widely available natural product, camptothecin.
