Cytotoxicities and structure-activity relationships of natural and unnatural lamellarins toward cancer cell lines.
Twenty-two naturally occurring and three unnatural lamellarins were synthesized and evaluated for their cytotoxicities against cancer cells. Across eleven cancer cell lines derived from six different cancer types, the IC(50) values of these compounds ranged from sub-nanomolar (0.08 nM) to micromolar (>97.0 microM). About one-fourth (6/25) and one-half (11/25) of these lamellarins are more potent than the positive control, etoposide, against at least six different cell lines and three different cell types, respectively. In general, lamellarins D, X, epsilon, M, N, and dehydrolamellarin J are significantly more potent than the other lamellarins. The IC(50) values were used to perform structure-activity relationship (SAR) studies by comparing the cytotoxic activities of several pairs of lamellarin structures that differ in selected substitution patterns. Our results not only reveal the importance of specific hydroxylation or methoxylation patterns for the first time, but also confirm prior findings and clarify some previous uncertainties.
Chittchang
Montakarn
M
Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Moo 4, Vibhavadee-Rangsit Highway, Laksi, Bangkok 10210, Thailand.
Batsomboon
Paratchata
P
Ruchirawat
Somsak
S
Ploypradith
Poonsakdi
P
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006900:Hydroxylation; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D003374:Coumarins; D006576:Heterocyclic Compounds, 4 or More Rings; D007546:Isoquinolines; C455554:lamellarin D; C489095:lamellarin epsilon