Quinonoid compounds via reactions of lawsone and 2-aminonaphthoquinone with α-bromonitroalkenes and nitroallylic acetates: Structural diversity by C-ring modification and cytotoxic evaluation against cancer cells

Thekke V Baiju; Renata G Almeida; Sudheesh T Sivanandan; Carlos A de Simone; Lucas M Brito; Bruno C Cavalcanti; Claudia Pessoa; Irishi N N Namboothiri; Eufrânio N da Silva Júnior

doi:10.1016/j.ejmech.2018.03.079

Quinonoid compounds via reactions of lawsone and 2-aminonaphthoquinone with α-bromonitroalkenes and nitroallylic acetates: Structural diversity by C-ring modification and cytotoxic evaluation against cancer cells

Eur J Med Chem. 2018 May 10:151:686-704. doi: 10.1016/j.ejmech.2018.03.079. Epub 2018 Apr 5.

Authors

Thekke V Baiju¹, Renata G Almeida², Sudheesh T Sivanandan¹, Carlos A de Simone³, Lucas M Brito⁴, Bruno C Cavalcanti⁴, Claudia Pessoa⁴, Irishi N N Namboothiri⁵, Eufrânio N da Silva Júnior⁶

Affiliations

¹ Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, 400 076, India.
² Institute of Exact Sciences, Department of Chemistry, Federal University of Minas Gerais, CEP, 31270-901, Belo Horizonte, MG, Brazil.
³ Department of Physics and Informatics, Institute of Physics, University of São Paulo, São Carlos, 13560-160, SP, Brazil.
⁴ Department of Physiology and Pharmacology, Federal University of Ceará, CEP, 60180-900, Fortaleza, CE, Brazil.
⁵ Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, 400 076, India. Electronic address: [email protected].
⁶ Institute of Exact Sciences, Department of Chemistry, Federal University of Minas Gerais, CEP, 31270-901, Belo Horizonte, MG, Brazil. Electronic address: [email protected].

PMID: 29660689
DOI: 10.1016/j.ejmech.2018.03.079

Abstract

Morita-Baylis-Hillman acetates and α-bromonitroalkenes have been employed in cascade reactions with lawsone and 2-aminonaphthoquinone for the one-pot synthesis of heterocycle fused quinonoid compounds. The reactions reported here utilized the 1,3-binucleophilic potential of hydroxy- and aminonaphthoquinones and the 1,2/1,3-bielectrophilic potential of bromonitroalkenes and Morita-Baylis-Hillman acetates for the synthesis of pyrrole and furan fused naphthoquinones. The synthesized compounds were evaluated against HCT-116 (human colon carcinoma cells), PC3 (human prostate cancer cells), HL-60 (human promyelocytic leukemia cells), SF295 (human glioblastoma cells) and NCI-H460 (human lung cancer cells) and exhibited antitumor activity with IC₅₀ values as low as < 2 μM. Selected compounds were also evaluated against OVCAR-8 (ovary), MX-1 (breast) and JURKAT (leukemia) cell lines. The cytotoxic potential of the quinones evaluated was also assayed using non-tumor cells, exemplified by peripheral blood mononuclear (PBMC) and L929 cells.

MeSH terms

Acetates / chemical synthesis
Acetates / chemistry
Alkenes / chemical synthesis
Alkenes / chemistry
Amination
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Chemistry Techniques, Synthetic
Furans / chemical synthesis
Furans / chemistry
Furans / pharmacology
Halogenation
Humans
Models, Molecular
Naphthoquinones / chemical synthesis
Naphthoquinones / chemistry
Neoplasms / drug therapy
Pyrroles / chemical synthesis
Pyrroles / chemistry*
Pyrroles / pharmacology*
Quinones / chemical synthesis
Quinones / chemistry*
Quinones / pharmacology*
Structure-Activity Relationship

Substances

Acetates
Alkenes
Antineoplastic Agents
Furans
Naphthoquinones
Pyrroles
Quinones
lawsone