Synthesis and cytotoxic activity of novel hexahydropyrrolo[2,3-b]indole imidazolium salts
- Bioorg Med Chem Lett. 2016 Jan 15;26(2):460-465. doi: 10.1016/j.bmcl.2015.11.092.
Affiliations
- 1. Key Laboratory of Medicinal Chemistry for Natural Resource (Yunnan University), Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China.
- 2. School of Chemistry & Environment, Engineering Research Center of Biopolymer Functional Materials of Yunnan, Yunnan Minzu University, Kunming 650500, PR China.
- 3. Key Laboratory of Medicinal Chemistry for Natural Resource (Yunnan University), Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China. Electronic address: [email protected].
- 4. Key Laboratory of Medicinal Chemistry for Natural Resource (Yunnan University), Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China. Electronic address: [email protected].
PMID: 26684853
DOI: 10.1016/j.bmcl.2015.11.092
Abstract
A series of novel hexahydropyrrolo[2,3-b]indole-1H-imidazolium salts were synthesized and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the 5,6-dimethyl-benzimidazole ring, and substitution of the imidazolyl-3-position with a 2-bromobenzyl or 2-naphthylmethyl group, were important for the cytotoxic activity. Notably, Compound 43, bearing a 2-bromobenzyl substituent at position-3 of 5,6-dimethyl-benzimidazole, was found to possess the most potent derivative against five human tumor cell lines with IC50 values below 2.68μM and more selective towards SMMC-7721, A549 and SW480 cell lines. Compounds 25 and 39 were more selective to HL-60 and MCF-7 cell lines with IC50 values of 0.47 and 1.46μM.
Keywords
Hexahydropyrrolo[2,3-b]indole; Imidazolium salts; Structure–activity relationships.