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In-silico studies and wet lab validation of Camptothecin derivatives for anti-cancer activity against liver (HepG2) and lung (A549) cancer cell lines

Author(s):

Komal Kalani, Dharmendra Kumar Yadav, Sarfaraz Alam, Feroz Khan, Mahendra P. Kashyap, Santosh Kumar Srivastava* and Aditya B. Pant  

Abstract:


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.

Keywords:

QSAR, ADME/T, bioavailability, docking, camptothecin derivatives, anticancer, cytotoxic.

Affiliation:

Medicinal Chemistry Department, CSIR-CIMAP, Lucknow-226015 (U.P.) , Metabolic & Structural Biology Department; CSIR-CIMAP, Lucknow-226015 (U.P.) , Metabolic & Structural Biology Department; CSIR-CIMAP, Lucknow-226015 (U.P.) , Metabolic & Structural Biology Department; CSIR-CIMAP, Lucknow-226015 (U.P.) , In vitro Toxicology Laboratory, CSIR-Indian Institute of Toxicology Research, Lucknow-226001, Medicinal Chemistry Department, CSIR-CIMAP, Lucknow-226015 (U.P.) , In vitro Toxicology Laboratory, CSIR-Indian Institute of Toxicology Research, Lucknow-226001



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