Novel approach to bis(indolyl)methanes: de novo synthesis of 1-hydroxyiminomethyl derivatives with anti-cancer properties

Carla Grosso; Ana Lúcia Cardoso; Américo Lemos; João Varela; Maria João Rodrigues; Luísa Custódio; Luísa Barreira; Teresa M V D Pinho e Melo

doi:10.1016/j.ejmech.2015.01.050

Novel approach to bis(indolyl)methanes: de novo synthesis of 1-hydroxyiminomethyl derivatives with anti-cancer properties

Eur J Med Chem. 2015 Mar 26:93:9-15. doi: 10.1016/j.ejmech.2015.01.050. Epub 2015 Jan 26.

Authors

Carla Grosso¹, Ana Lúcia Cardoso², Américo Lemos³, João Varela⁴, Maria João Rodrigues⁴, Luísa Custódio⁴, Luísa Barreira⁴, Teresa M V D Pinho e Melo⁵

Affiliations

¹ Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal; CIQA, FCT, University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal.
² Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal.
³ CIQA, FCT, University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal. Electronic address: alemos@ualg.pt.
⁴ CCMAR-Centre of Marine Sciences, Faculty of Sciences and Technology, University of Algarve, Ed. 7, Campus of Gambelas, Faro 8005-139, Portugal.
⁵ Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal. Electronic address: tmelo@ci.uc.pt.

PMID: 25644672
DOI: 10.1016/j.ejmech.2015.01.050

Abstract

A versatile and broad range approach to previously unknown bis(indolyl)methane oximes based on two consecutive hetero Diels-Alder cycloaddition reactions of electrophilic conjugated nitrosoalkenes with indoles is disclosed. The cytotoxic properties and selectivity of some adducts against several human cancer cell lines pointing to a promising role in the development of anti-tumoural drugs, in particular for leukaemia and lymphoma.

Keywords: Anti-cancer activity; Bis(indolyl)methanes; Indoles; Leukaemia; Lymphoma; Nitrosoalkenes.

Publication types

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

MeSH terms

Animals
Antineoplastic Agents / adverse effects
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Cell Culture Techniques
Cell Line, Tumor
Cell Survival / drug effects
Cycloaddition Reaction
Drug Design*
Humans
Indoles / adverse effects
Indoles / chemical synthesis*
Indoles / chemistry
Indoles / pharmacology
Macrophages / drug effects
Microglia / drug effects
Oximes / adverse effects
Oximes / chemical synthesis*
Oximes / chemistry
Oximes / pharmacology
Structure-Activity Relationship

Substances

Antineoplastic Agents
Indoles
Oximes