In Vitro Antimicrobial Activity of Isopimarane-Type Diterpenoids

• Main Authors: Vera M. S. Isca, Joana Andrade, Ana Sofia Fernandes, Paulo Paixão, Clara Uriel, Ana María Gómez, Noélia Duarte, Patrícia Rijo
• Format: Article
• Language: English
• Published: MDPI AG 2020-09-01
• Series: Molecules
• Subjects: isopimaranes; antimicrobial; MDA-MB-231 cells
• Online Access: https://www.mdpi.com/1420-3049/25/18/4250
• ISSN: 1420-3049

The antimicrobial evaluation of twelve natural and hemisynthetic isopimarane diterpenes are reported. The compounds were evaluated against a panel of Gram-positive bacteria, including two methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) strains and one vancomycin-resistant <i>Enterococcus</i> (VRE) strain. Only natural compounds 7,15-isopimaradien-19-ol (<b>1</b>) and 19-acetoxy-7,15-isopimaradien-3β-ol (<b>6</b>) showed promising results. Isopimarane (<b>1</b>) was the most active, showing MIC values between 6.76 µM against <i>S. aureus</i> (ATCC 43866) and 216.62 µM against <i>E. faecalis</i> (FFHB 427483) and <i>E. flavescens</i> (ATCC 49996). Compound (<b>6</b>) showed moderated activity against all tested microorganisms (MIC between value 22.54 and 45.07 µM). These compounds were found to be active against the methicillin-sensitive strains of <i>S. aureus</i> (CIP 106760 and FFHB 29593), showing MIC values of 13.55 (<b>1</b>) and 22.54 (<b>6</b>) µM. Both compounds were also active against vancomycin-resistant <i>E. faecalis</i> (ATCC 51299) (MIC values of 54.14 and 45.07 µM, respectively). In addition, the cytotoxicity of nine compounds 7,15-isopimaradien-3β,19-diol (<b>2</b>); mixture: 15-isopimarene-8β-isobutyryloxy-19-ol and 15-isopimarene-8β-butyryloxy-19-ol (<b>3</b>); 3β-acetoxy-7,15-isopimaradiene-19-ol (<b>5</b>); 19-acetoxy-7,15-isopimaradiene-3β-ol (<b>6</b>); 3β,19-diacetoxy-7,15-isopimaradiene (<b>8</b>); 15-isopimarene-8β,19-diol (<b>9</b>); 19-<i>O</i>-β-<span style="font-variant: small-caps;">d</span>-glucopyranoside-7,15-isopimaradiene (<b>10</b>); lagascatriol-16-<i>O</i>-β-<span style="font-variant: small-caps;">d</span>-glucopyranoside (<b>11</b>) and lagascatriol-16-<i>O</i>-α-<span style="font-variant: small-caps;">d</span>-mannopyranoside (<b>12</b>) was evaluated in the human breast cancer cell line MDA-MB-231. Isopimarane (<b>2</b>) was the only compound showing some cytotoxicity. The IC₅₀ value of compound (<b>2</b>) was 15 µM, suggesting a mild antiproliferative activity against these breast cancer cells.