Synthesis of Selenium-Quinone Hybrid Compounds with Potential Antitumor Activity via Rh-Catalyzed C-H Bond Activation and Click Reactions

Guilherme A M Jardim; Daisy J B Lima; Wagner O Valença; Daisy J B Lima; Bruno C Cavalcanti; Claudia Pessoa; Jamal Rafique; Antonio L Braga; Claus Jacob; Eufrânio N da Silva Júnior; Eduardo H G da Cruz

doi:10.3390/molecules23010083

Synthesis of Selenium-Quinone Hybrid Compounds with Potential Antitumor Activity via Rh-Catalyzed C-H Bond Activation and Click Reactions

Molecules. 2017 Dec 30;23(1):83. doi: 10.3390/molecules23010083.

Authors

Affiliations

¹ Department of Chemistry, Institute of Exact Sciences, Federal University of Minas Gerais, UFMG, 31270-901 Belo Horizonte, Brazil. [email protected].
² Department of Physiology and Pharmacology, Federal University of Ceará, CEP 60180-900 Fortaleza, Brazil. [email protected].
³ Department of Chemistry, Institute of Exact Sciences, Federal University of Minas Gerais, UFMG, 31270-901 Belo Horizonte, Brazil. [email protected].
⁴ Department of Physiology and Pharmacology, Federal University of Ceará, CEP 60180-900 Fortaleza, Brazil. [email protected].
⁵ Department of Physiology and Pharmacology, Federal University of Ceará, CEP 60180-900 Fortaleza, Brazil. [email protected].
⁶ Department of Chemistry, Federal University of Santa Catarina, 88040-900 Florianópolis, Brazil. [email protected].
⁷ Department of Chemistry, Federal University of Santa Catarina, 88040-900 Florianópolis, Brazil. [email protected].
⁸ Division of Bioorganic Chemistry, Department of Pharmacy, University of Saarland, Campus B2 1, D-66123 Saarbruecken, Germany. [email protected].
⁹ Department of Chemistry, Institute of Exact Sciences, Federal University of Minas Gerais, UFMG, 31270-901 Belo Horizonte, Brazil. [email protected].
¹⁰ Department of Chemistry, Institute of Exact Sciences, Federal University of Minas Gerais, UFMG, 31270-901 Belo Horizonte, Brazil. [email protected].
¹¹ Division of Bioorganic Chemistry, Department of Pharmacy, University of Saarland, Campus B2 1, D-66123 Saarbruecken, Germany. [email protected].

Abstract

In continuation of our quest for new redox-modulating catalytic antitumor molecules, selenium-containing quinone-based 1,2,3-triazoles were synthesized using rhodium-catalyzed C-H bond activation and click reactions. All compounds were evaluated against five types of cancer cell lines: HL-60 (human promyelocytic leukemia cells), HCT-116 (human colon carcinoma cells), SF295 (human glioblastoma cells), NCIH-460 (human lung cells) and PC3 (human prostate cancer cells). Some compounds showed good activity with IC₅₀ values below 1 µM. The cytotoxic potential of the naphthoquinoidal derivatives was also evaluated in non-tumor cells, exemplified by L929 cells. Overall, these compounds represent promising new lead derivatives and stand for a new class of chalcogenium-containing derivatives with potential antitumor activity.

Keywords: C-H activation; cancer; click chemistry; lapachol; naphthoquinone; selenium.

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / therapeutic use
Catalysis
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Click Chemistry
Drug Screening Assays, Antitumor
Humans
Organoselenium Compounds / chemical synthesis*
Organoselenium Compounds / pharmacology
Quinones / chemistry*
Rhodium / chemistry*
Structure-Activity Relationship
Triazoles / chemical synthesis*
Triazoles / pharmacology

Substances

Antineoplastic Agents
Organoselenium Compounds
Quinones
Triazoles
Rhodium