Chalcogen containing heterocyclic scaffolds: New hybrids with antitumoral activity

Verónica Alcolea, Daniel Plano, Ignacio Encío, Juan Antonio Palop, Arun Sharma, Carmen Sanmartín

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

In this work, 27 novel hybrid derivatives containing diverse substituents with chalcogen atoms (selenium or sulfur) and several active heterocyclic scaffolds have been synthesized. Compounds were tested against two human cancer cells lines (MCF7 and PC-3) and a normal human mammary epithelial cell line (184B5) in order to determine their activity and selectivity against malignant cells. Ten compounds showed GI50values below 10 μM in at least one of the cancer cell lines and six of them exhibited a selectivity index higher than 9. In general, selenium-containing compounds were more active than their corresponding sulfur analogs but we found some thiocyanate derivatives with comparable or higher activity and selectivity. Among the different substituents, the seleno- and thio-cyanate groups showed the most promising results. On the basis of their potent activity and high selectivity index, compounds 7e and 8f (containing a thiocyanate and a selenocyanate group, respectively) were selected for further biological evaluation. Both the compounds induced caspase-dependent cell death and cell cycle arrest in G2/M phase. In addition, these compounds do not violate any of the Lipinski's Rule of Five and thus possess good potential to become drugs, compound 7e being particularly promising.

Original languageEnglish (US)
Pages (from-to)407-418
Number of pages12
JournalEuropean Journal of Medicinal Chemistry
Volume123
DOIs
StatePublished - Jan 1 2016

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Chalcogens
Scaffolds
Cells
Selenium
Sulfur
Cell Line
Selenium Compounds
Cyanates
Derivatives
G2 Phase
Cell death
Caspases
Cell Cycle Checkpoints
Cell Division
Neoplasms
Breast
Cell Death
Epithelial Cells
Atoms
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Alcolea, Verónica ; Plano, Daniel ; Encío, Ignacio ; Palop, Juan Antonio ; Sharma, Arun ; Sanmartín, Carmen. / Chalcogen containing heterocyclic scaffolds : New hybrids with antitumoral activity. In: European Journal of Medicinal Chemistry. 2016 ; Vol. 123. pp. 407-418.
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Chalcogen containing heterocyclic scaffolds : New hybrids with antitumoral activity. / Alcolea, Verónica; Plano, Daniel; Encío, Ignacio; Palop, Juan Antonio; Sharma, Arun; Sanmartín, Carmen.

In: European Journal of Medicinal Chemistry, Vol. 123, 01.01.2016, p. 407-418.

Research output: Contribution to journalArticle

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