喜树碱
生物信息学
数量结构-活动关系
拓扑异构酶
对接(动物)
化学
计算生物学
肺癌
A549电池
立体化学
药理学
体外
组合化学
生物化学
生物
医学
肿瘤科
基因
护理部
作者
Komal Kalani,Dharmendra Kumar Yadav,Sarfaraz Alam,Feroz Khan,Mahendra Kashyap,Santosh K. Srivastava,Aditya B. Pant
标识
DOI:10.2174/1568026621666210426124719
摘要
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 the multiple linear regression (MLR) method followed by ADMET and docking studies. The regression coefficient (r 2 ) and cross-validation regression coefficients (rCV 2T ) 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.
科研通智能强力驱动
Strongly Powered by AbleSci AI