: 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 the multiple linear regression
(MLR) method followed by ADMET and docking studies. The regression coefficient (r2
cross-validation regression coefficients (rCV2T
) of the QSAR model for the HepG2 cell line was
0.95 and 0.90, respectively, and for the 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 are consistent 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.