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Keywords:

  • cancer;
  • inhibitor;
  • lamellarin;
  • multidrug resistance;
  • p-glycoprotein

Abstract

Chemical analysis of a Didemnum sp. (CMB-01656) collected during scientific Scuba operations off Wasp Island, New South Wales, yielded five new lamellarins A1 (1), A2 (2), A3 (3), A4 (4) and A5 (5) and eight known lamellarins C (6), E (7), K (8), M (9), S (10), T (11), X (12) and χ (13). Analysis of a second Didemnum sp. (CMB-02127) collected during scientific trawling operations along the Northern Rottnest Shelf, Western Australia, yielded the new lamellarin A6 (14) and two known lamellarins G (15) and Z (16). Structures were assigned to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 on the basis of detailed spectroscopic analysis with comparison to literature data and authentic samples. Access to this unique library of natural lamellarins (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16) provided a rare opportunity for structure–activity relationship (SAR) investigations, probing interactions between lamellarins and the ABC transporter efflux pump P-glycoprotein (P-gp) with a view to reversing multidrug resistance in a human colon cancer cell line (SW620 Ad300). These SAR studies, which were expanded to include the permethylated lamellarin derivative (17) and a series of lamellarin-inspired synthetic coumarins (19, 20, 21, 22, 23, 24) and isoquinolines (25, 26), successfully revealed 17 as a promising new non-cytotoxic P-gp inhibitor pharmacophore.

Featured Compounds

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  1. 1 - 26
Compound 1
Molecular Weight:487.4575
Molecular Formula:C27H21NO8
InChIKey:UFKVDBMLXATCKW-UHFFFAOYSA-N
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Compound 2
Molecular Weight:517.4835
Molecular Formula:C28H23NO9
InChIKey:IWHHJJNEKAPOEW-UHFFFAOYSA-N
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Compound 3
Molecular Weight:515.5107
Molecular Formula:C29H25NO8
InChIKey:GZKQBRWRBDJJBB-UHFFFAOYSA-N
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Compound 4
Molecular Weight:459.4044
Molecular Formula:C25H17NO8
InChIKey:MEVCOCREBASNGU-UHFFFAOYSA-N
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Compound 5
Molecular Weight:471.4151
Molecular Formula:C26H17NO8
InChIKey:PYYBNNNSEIYUEH-UHFFFAOYSA-N
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Compound 6
Molecular Weight:545.5367
Molecular Formula:C30H27NO9
InChIKey:ZCBPXPBGAXIGDM-UHFFFAOYSA-N
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Compound 7
Molecular Weight:531.5101
Molecular Formula:C29H25NO9
InChIKey:JAYUXAMNSNMXCO-UHFFFAOYSA-N
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Compound 8
Molecular Weight:531.5101
Molecular Formula:C29H25NO9
InChIKey:CVWRVFSYXZNUEG-UHFFFAOYSA-N
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Compound 9
Molecular Weight:529.4942
Molecular Formula:C29H23NO9
InChIKey:NTKJJSXQSXRFMC-UHFFFAOYSA-N
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Compound 10
Molecular Weight:473.431
Molecular Formula:C26H19NO8
InChIKey:DLWXEJKAEMFNEO-UHFFFAOYSA-N
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Compound 11
Molecular Weight:545.5367
Molecular Formula:C30H27NO9
InChIKey:NKDLSUHQYRACEX-UHFFFAOYSA-N
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Compound 12
Molecular Weight:529.4942
Molecular Formula:C29H23NO9
InChIKey:PZCRTZSRUGAIBP-UHFFFAOYSA-N
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Compound 13
Molecular Weight:501.4841
Molecular Formula:C28H23NO8
InChIKey:Not Available
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Compound 14
Molecular Weight:501.4841
Molecular Formula:C28H23NO8
InChIKey:BILSMFOVHOUADI-UHFFFAOYSA-N
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Compound 15
Molecular Weight:501.4841
Molecular Formula:C28H23NO8
InChIKey:JOMAOYFMBLTSQC-UHFFFAOYSA-N
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Compound 16
Molecular Weight:487.4575
Molecular Formula:C27H21NO8
InChIKey:PCWYFKMEMPTOQC-UHFFFAOYSA-N
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Compound 17
Molecular Weight:543.5639
Molecular Formula:C31H29NO8
InChIKey:RUEGDDQFHWOGAK-UHFFFAOYSA-N
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Compound 19
Molecular Weight:162.1421
Molecular Formula:C9H6O3
InChIKey:ORHBXUUXSCNDEV-UHFFFAOYSA-N
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Compound 20
Molecular Weight:176.1687
Molecular Formula:C10H8O3
InChIKey:LIIALPBMIOVAHH-UHFFFAOYSA-N
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Compound 21
Molecular Weight:178.1415
Molecular Formula:C9H6O4
InChIKey:ILEDWLMCKZNDJK-UHFFFAOYSA-N
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Compound 22
Molecular Weight:192.1681
Molecular Formula:C10H8O4
InChIKey:SYTYLPHCLSSCOJ-UHFFFAOYSA-N
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Compound 23
Molecular Weight:192.1681
Molecular Formula:C10H8O4
InChIKey:RODXRVNMMDRFIK-UHFFFAOYSA-N
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Compound 24
Molecular Weight:206.1947
Molecular Formula:C11H10O4
InChIKey:GUAFOGOEJLSQBT-UHFFFAOYSA-N
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Compound 25
Molecular Weight:246.101
Molecular Formula:C9H12BrNO2
InChIKey:LBDAQUYUIYKBKJ-UHFFFAOYSA-N
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Compound 26
Molecular Weight:229.703
Molecular Formula:C11H16ClNO2
InChIKey:SHOWAGCIRTUYNA-UHFFFAOYSA-N
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Compound 18
Molecular Weight:559.5633
Molecular Formula:C31H29NO9
InChIKey:LIVLXJLCXACUMU-UHFFFAOYSA-N
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