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

• Published in: Marine drugs Vol. 20; no. 4; p. 265
• Main Authors: Kovalerchik, Dimitry, Zovko, Ana, Hååg, Petra, Sierakowiak, Adam, Viktorsson, Kristina, Lewensohn, Rolf, Ilan, Micha, Carmeli, Shmuel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13-04-2022; MDPI
• Subjects: Acetylene; Acetylene - therapeutic use; Alcohol; Alcohols; Alkanes; alkylynols; Analogs; Antineoplastic Agents - chemistry; Cancer; Carbon; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - metabolism; Cells; Chain branching; Chains; Cribrochalina vasculum; Cytotoxicity; Diploids; Fibroblasts; Humans; Lipids; Lung cancer; Lung carcinoma; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lungs; Medicin och hälsovetenskap; Metabolites; natural product; Neoplasms; Non-small cell lung carcinoma; Selectivity; Small cell lung carcinoma; sponge; Structure-Activity Relationship; Toxicity testing; Tumors; Cribrochalina vasculum; sponge; alkylynols; non-small cell lung carcinoma; natural product; cytotoxicity
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md20040265

A series of twenty-three linear and branched chain mono acetylene lipids were isolated from the Caribbean Sea sponge
. Seventeen of the compounds,
, are new, while six,
, were previously characterized from the same sponge. Some of the new acetylene-3-hydroxy alkanes
,
,
,
,
were tested for selective cytotoxicity in non-small cell lung carcinoma (NSCLC) cells over WI-38 normal diploid lung fibroblasts. Compound
, presented clear tumor selective activity while,
and
, showed selectivity at lower doses and
and
, were not active towards NSCLC cells at all. The earlier reported selective cytotoxicity of some acetylene-3-hydroxy alkanes (
and
), in NSCLC cells and/or other tumor cell types were also confirmed for
,
and
. To further study the structure activity relationships (SAR) of this group of compounds, we synthesized several derivatives of acetylene-3-hydroxy alkanes,
-
,
-
,
-
,
-
,
-
,
-
,
-
,
-
,
-
,
-
,
-
,
-
,
-
and
-
, along with other 3-substituted derivatives,
-
,
-
,
-
,
-
,
-
and
-
, and assessed their cytotoxic activity against NSCLC cells and diploid fibroblasts. SAR studies revealed that the alcohol moiety at position 3 and its absolute
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.