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Bioorg Med Chem Lett. 2018 Feb 15;28(4):589-593. doi: 10.1016/j.bmcl.2018.01.041. Epub 2018 Feb 2.

Synthetic analogues of the montanine-type alkaloids with activity against apoptosis-resistant cancer cells.

Author information

1
Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, United States.
2
Laboratoire de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Brussels, Belgium.
3
Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, United States.
4
Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Complesso Universitario Monte Sant'Angelo, Via Cintia 4, 80126 Napoli, Italy.
5
Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, United States. Electronic address: a_k76@txstate.edu.

Abstract

In a search of small molecules active against apoptosis-resistant cancer cells, a skeletal rearrangement of alkaloid haemanthamine was utilized to generate a series of compounds possessing the alkaloid montanine ring system. The synthesized compounds were found to inhibit proliferation of cancer cells resistant to apoptosis at micromolar concentrations. Selected compounds were also active against patient-derived glioblastoma cells expressing stem-cell markers. This is the first report describing the preparation of synthetic analogues of the montanine-type alkaloids with antiproliferative activity. The compounds prepared in the current investigation appear to be a useful starting point for the development of agents to fight cancers with apoptosis resistance, and thus, associated with poor prognoses.

KEYWORDS:

Antiproliferative activity; Apoptosis resistance; Haemanthamine; Manthine; Montanine

PMID:
29409754
PMCID:
PMC5831727
DOI:
10.1016/j.bmcl.2018.01.041
[Indexed for MEDLINE]
Free PMC Article

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