Smenamide a analogues. Synthesis and biological activity on multiple myeloma cells

Alessia Caso, Ilaria Laurenzana, Daniela Lamorte, Stefania Trino, Germana Esposito, Vincenzo Piccialli, Valeria Costantino

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Smenamides are an intriguing class of peptide/polyketide molecules of marine origin showing antiproliferative activity against lung cancer Calu-1 cells at nanomolar concentrations through a clear pro-apoptotic mechanism. To probe the role of the activity-determining structural features, the 16-epi-analogue of smenamide A and eight simplified analogues in the 16-epi series were prepared using a flexible synthetic route. The synthetic analogues were tested on multiple myeloma (MM) cell lines showing that the configuration at C-16 slightly affects the activity, since the 16-epi-derivative is still active at nanomolar concentrations. Interestingly, it was found that the truncated compound 8, mainly composed of the pyrrolinone terminus, was not active, while compound 13, essentially lacking the pyrrolinone moiety, was 1000-fold less active than the intact substance and was the most active among all the synthesized compounds.

Original languageEnglish
Article number206
JournalMarine Drugs
Volume16
Issue number6
DOIs
Publication statusPublished - Jun 1 2018

Fingerprint

Polyketides
Multiple Myeloma
Lung Neoplasms
Cell Line
Peptides

Keywords

  • Antiproliferative activity
  • Functional-analogues
  • Marine natural products
  • MM cell line
  • Peptide/polyketide molecules
  • Smenamides
  • Synthetic analogues

ASJC Scopus subject areas

  • Drug Discovery

Cite this

Caso, A., Laurenzana, I., Lamorte, D., Trino, S., Esposito, G., Piccialli, V., & Costantino, V. (2018). Smenamide a analogues. Synthesis and biological activity on multiple myeloma cells. Marine Drugs, 16(6), [206]. https://doi.org/10.3390/md16060206

Smenamide a analogues. Synthesis and biological activity on multiple myeloma cells. / Caso, Alessia; Laurenzana, Ilaria; Lamorte, Daniela; Trino, Stefania; Esposito, Germana; Piccialli, Vincenzo; Costantino, Valeria.

In: Marine Drugs, Vol. 16, No. 6, 206, 01.06.2018.

Research output: Contribution to journalArticle

Caso, A, Laurenzana, I, Lamorte, D, Trino, S, Esposito, G, Piccialli, V & Costantino, V 2018, 'Smenamide a analogues. Synthesis and biological activity on multiple myeloma cells', Marine Drugs, vol. 16, no. 6, 206. https://doi.org/10.3390/md16060206
Caso A, Laurenzana I, Lamorte D, Trino S, Esposito G, Piccialli V et al. Smenamide a analogues. Synthesis and biological activity on multiple myeloma cells. Marine Drugs. 2018 Jun 1;16(6). 206. https://doi.org/10.3390/md16060206
Caso, Alessia ; Laurenzana, Ilaria ; Lamorte, Daniela ; Trino, Stefania ; Esposito, Germana ; Piccialli, Vincenzo ; Costantino, Valeria. / Smenamide a analogues. Synthesis and biological activity on multiple myeloma cells. In: Marine Drugs. 2018 ; Vol. 16, No. 6.
@article{568714533ba84e4bb2626b89aba5dbf8,
title = "Smenamide a analogues. Synthesis and biological activity on multiple myeloma cells",
abstract = "Smenamides are an intriguing class of peptide/polyketide molecules of marine origin showing antiproliferative activity against lung cancer Calu-1 cells at nanomolar concentrations through a clear pro-apoptotic mechanism. To probe the role of the activity-determining structural features, the 16-epi-analogue of smenamide A and eight simplified analogues in the 16-epi series were prepared using a flexible synthetic route. The synthetic analogues were tested on multiple myeloma (MM) cell lines showing that the configuration at C-16 slightly affects the activity, since the 16-epi-derivative is still active at nanomolar concentrations. Interestingly, it was found that the truncated compound 8, mainly composed of the pyrrolinone terminus, was not active, while compound 13, essentially lacking the pyrrolinone moiety, was 1000-fold less active than the intact substance and was the most active among all the synthesized compounds.",
keywords = "Antiproliferative activity, Functional-analogues, Marine natural products, MM cell line, Peptide/polyketide molecules, Smenamides, Synthetic analogues",
author = "Alessia Caso and Ilaria Laurenzana and Daniela Lamorte and Stefania Trino and Germana Esposito and Vincenzo Piccialli and Valeria Costantino",
year = "2018",
month = "6",
day = "1",
doi = "10.3390/md16060206",
language = "English",
volume = "16",
journal = "Marine Drugs",
issn = "1660-3397",
publisher = "MDPI AG",
number = "6",

}

TY - JOUR

T1 - Smenamide a analogues. Synthesis and biological activity on multiple myeloma cells

AU - Caso, Alessia

AU - Laurenzana, Ilaria

AU - Lamorte, Daniela

AU - Trino, Stefania

AU - Esposito, Germana

AU - Piccialli, Vincenzo

AU - Costantino, Valeria

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Smenamides are an intriguing class of peptide/polyketide molecules of marine origin showing antiproliferative activity against lung cancer Calu-1 cells at nanomolar concentrations through a clear pro-apoptotic mechanism. To probe the role of the activity-determining structural features, the 16-epi-analogue of smenamide A and eight simplified analogues in the 16-epi series were prepared using a flexible synthetic route. The synthetic analogues were tested on multiple myeloma (MM) cell lines showing that the configuration at C-16 slightly affects the activity, since the 16-epi-derivative is still active at nanomolar concentrations. Interestingly, it was found that the truncated compound 8, mainly composed of the pyrrolinone terminus, was not active, while compound 13, essentially lacking the pyrrolinone moiety, was 1000-fold less active than the intact substance and was the most active among all the synthesized compounds.

AB - Smenamides are an intriguing class of peptide/polyketide molecules of marine origin showing antiproliferative activity against lung cancer Calu-1 cells at nanomolar concentrations through a clear pro-apoptotic mechanism. To probe the role of the activity-determining structural features, the 16-epi-analogue of smenamide A and eight simplified analogues in the 16-epi series were prepared using a flexible synthetic route. The synthetic analogues were tested on multiple myeloma (MM) cell lines showing that the configuration at C-16 slightly affects the activity, since the 16-epi-derivative is still active at nanomolar concentrations. Interestingly, it was found that the truncated compound 8, mainly composed of the pyrrolinone terminus, was not active, while compound 13, essentially lacking the pyrrolinone moiety, was 1000-fold less active than the intact substance and was the most active among all the synthesized compounds.

KW - Antiproliferative activity

KW - Functional-analogues

KW - Marine natural products

KW - MM cell line

KW - Peptide/polyketide molecules

KW - Smenamides

KW - Synthetic analogues

UR - http://www.scopus.com/inward/record.url?scp=85048965388&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048965388&partnerID=8YFLogxK

U2 - 10.3390/md16060206

DO - 10.3390/md16060206

M3 - Article

VL - 16

JO - Marine Drugs

JF - Marine Drugs

SN - 1660-3397

IS - 6

M1 - 206

ER -