Cytotoxic Alkylynols of the Sponge Cribrochalina vasculum: Structure, Synthetic Analogs and SAR Studies

Dimitry Kovalerchik, Ana Zovko, Petra Hååg, Adam Sierakowiak, Kristina Viktorsson, Rolf Lewensohn, Micha Ilan, Shmuel Carmeli*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

A series of twenty‐three linear and branched chain mono acetylene lipids were isolated from the Caribbean Sea sponge Cribrochalina vasculum. Seventeen of the compounds, 1–17, are new, while six, 18–23, were previously characterized from the same sponge. Some of the new acetylene‐ 3‐hydroxy alkanes 1, 6, 7, 8, 10 were tested for selective cytotoxicity in non‐small cell lung carcinoma (NSCLC) cells over WI‐38 normal diploid lung fibroblasts. Compound 7, presented clear tumor selective activity while, 1 and 8, showed selectivity at lower doses and 6 and 10, were not active to-wards NSCLC cells at all. The earlier reported selective cytotoxicity of some acetylene‐3‐hydroxy alkanes (scal‐18 and 23), in NSCLC cells and/or other tumor cell types were also confirmed for 19, 20 and 22. To further study the structure activity relationships (SAR) of this group of compounds, we synthesized several derivatives of acetylene‐3‐hydroxy alkanes, rac‐18, scal‐S‐18, R‐18, rac‐27, rac‐32, R‐32, S‐32, rac‐33, rac‐41, rac‐42, rac‐43, rac‐45, rac‐48 and rac‐49, along with other 3‐substi-tuted derivatives, rac‐35, rac‐36, rac‐37, rac‐38, rac‐39 and rac‐40, and assessed their cytotoxic activity against NSCLC cells and diploid fibroblasts. SAR studies revealed that the alcohol moiety at position 3 and its absolute R configuration both were essential for the tumor cell line selective activity while for its cytotoxic magnitude the alkyl chain length and branching were of less significance.

Original languageEnglish
Article number265
JournalMarine Drugs
Volume20
Issue number4
DOIs
StatePublished - Apr 2022

Funding

FundersFunder number
Karolinska FOUU
School of Chemistry
Stiftelsen f?r Hematologisk Forskning och Kvalitetss?kring
Stiftelsen för Hematologisk Forskning och Kvalitetssäkring2017/180218
European CommissionPF7/2007‐2013, 266033, KBBE‐2010‐266033
CancerfondenCAN 2018/597, CAN 2015/401
Stockholms Läns Landsting
Cancerföreningen i Stockholm2‐2792/2017, 191293, 171123, 201202, 4‐ 1989/2020

    Keywords

    • Cribrochalina vasculum
    • alkylynols
    • cytotoxicity
    • natural product
    • non‐small cell lung carcinoma
    • sponge

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