Diversity-oriented TsOH catalysis-enabled construction of tanshinone-substituted bis(indolyl/pyrrolyl)methanes and their biological evaluation for anticancer activities

ABSTRACT

We have developed an efficient and straightforward methodology for the synthesis of novel tanshinone-substituted bis(indolyl/pyrrolyl)methane scaffolds 3 through TsOH catalysis-enabled addition of indoles or pyrroles 1 with tanshinones 2 based on molecular hybridization strategy. Products were smoothly obtained in good yields (up to 81% yield). This protocol also represents the first construction of tanshinone skeleton-fused bis(indolyl/pyrrolyl)methane scaffolds, thus leading to new knowledge in the fields of both molecular complexity and diversity-oriented synthesis and the lead compound discovery. Furthermore, their biological activities against human leukemia cells K562, human prostate cancer cells PC-3, and human lung cancer cells A549 have been preliminarily demonstrated by in vitro assays. The results demonstrated that most of these compounds 3 obtained by this protocol showed comparable activity to the positive control of cisplatin.

GRAPHICAL ABSTRACT

KEYWORDS:

• Antitumor activity
• bis(indolyl/pyrrolyl)methanes
• molecular hybridization
• tanshinone
• TsOH

Acknowledgments

We are grateful for the financial support from the National Natural Science Foundations of China (No. 81660576, No. 81560563, No. 81760625 and No. 81603390); Excellent creative talents of guizhou province (Qian Jiao He KY Zi [(2015)491] and Qian Ke He Zi [2015]4032, [2017]5609); Guizhou Chinese medicine and pharmaceutical engineering professional degree graduate student workstation (JYSZ [2014]002); Project of Guizhou province (Qian Ke He Zi ([2016]5623 and [2015]4010) and Major project of the graduate student education teaching reform (Qian Jiao Yan He JG Zi)[2016]06.

Additional information

Funding

This work was supported by the National Natural Science Foundations of China [Grant Numbers 81560563, 81660576, 81760625 and 81603390].