A thiol-inducible and quick-response DNA cross-linking agent

Yuanzhen Xu; Hongbo Wei; Jianjun Chen; Kun Gao

doi:10.1016/j.bmcl.2018.11.040

A thiol-inducible and quick-response DNA cross-linking agent

Bioorg Med Chem Lett. 2019 Jan 15;29(2):281-283. doi: 10.1016/j.bmcl.2018.11.040. Epub 2018 Nov 19.

Authors

Yuanzhen Xu¹, Hongbo Wei², Jianjun Chen³, Kun Gao⁴

Affiliations

¹ State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Gansu, Lanzhou 730000, China; Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Shaanxi, Yangling 712100, China.
² Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Shaanxi, Yangling 712100, China.
³ State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Gansu, Lanzhou 730000, China.
⁴ State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Gansu, Lanzhou 730000, China. Electronic address: npchem@lzu.edu.cn.

PMID: 30473177
DOI: 10.1016/j.bmcl.2018.11.040

Abstract

Three new 2,4-dinitrobenzenesulfonyl derivatives 1-3 were successfully prepared for the first time using a simple process. They were efficiently triggered by thiols (glutathione and l-cysteine) to release the corresponding phenol derivatives (4-6) within 5 min. The quick response of 1-3 toward thiols was determined by ¹H NMR and HPLC. Moreover, our results indicated that 1 could induce DNA cross-linking in the presence of glutathione, probably due to the quinone methide formation of phenol intermediate 4 followed by departure of 2,4-dinitrobenzenesulfonyl group.

Keywords: 2,4-Dinitrobenzenesulfonyl; Antitumor agents; DNA cross-linking; Quinone methide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Benzenesulfonates / chemistry*
Cross-Linking Reagents / chemistry*
DNA / chemistry*
Dose-Response Relationship, Drug
Molecular Structure
Structure-Activity Relationship
Sulfhydryl Compounds / chemistry*

Substances

Benzenesulfonates
Cross-Linking Reagents
Sulfhydryl Compounds
2,4-dinitrobenzenesulfonic acid
DNA