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Clathrolides A–B: previously undescribed macrocylic lactones from marine demosponge Clathria (Thalysias) vulpina (Lamarck, 1814) as potential antihypertensive leads attenuating angiotensin converting enzyme

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Abstract

Biochemical investigation of bioactive compounds from the marine demospongiae Clathria (Thalysias) vulpina (Lamarck, 1814) (family Microcionidae) resulted in the isolation of two previously undescribed 22-membered macrocyclic lactone derivatives clathrolide A and B from its organic extract. Structural elucidation of the compounds were carried out using spectroscopic analysis. Clathrolide A exhibited greater antihypertensive (IC50 0.44 ± 0.02 mM), anti-inflammatory (IC50 0.74 ± 0.04 mM), anti-hyperglycemic (IC50 0.85 ± 0.01 mM), and antioxidant (IC50 0.70 ± 0.03 mM) activities compared to clathrolide B. Among various bioactivities, such as antihypertensive, anti-inflammatory, anti-hyperglycemic, and antioxidant properties, angiotensin converting enzyme attenuation potential of clathrolide A was found to be significantly greater, and comparable with the standard antihypertensive drug, captopril (IC50 0.36 ± 0.03 mM). Higher electronic properties (topological polar surface area 133.52) along with comparatively lesser docking score and binding energy of clathrolide A with the aminoacyl residues of angiotensin-I converting enzyme (−12.38 and −12.91 kcal/mol, respectively) recognized its prospective inhibitory property against the enzyme catalyzing the rate-limiting step to form the vasoconstrictor angiotensin-II.

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The chromatographic and spectroscopic spectral data are included as Supplementary item.

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Acknowledgements

The authors gratefully acknowledge the funding by the Indian Council of Agricultural Research (ICAR, New Delhi, India) under Central Marine Fisheries Research Institute (ICAR-CMFRI) project “Development of Bioactive Pharmacophores from Marine Organisms” (MBT/HLT/SUB23). The authors are grateful to the Director, ICAR-CMFRI, and Head, Marine Biotechnology Division of ICAR-CMFRI for facilitating the research activities. The authors are thankful to the Chairman, Department of Chemistry, Mangalore University (Karnataka, India) for providing with necessary support.

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  1. These authors contributed equally: Prima Francis, Kajal Chakraborty

Authors and Affiliations

  1. Marine Biotechnology Division, Central Marine Fisheries Research Institute, Ernakulam North, P.B. No. 1603, Cochin, Kerala, 682018, India

    Prima Francis & Kajal Chakraborty

  2. Department of Chemistry, Mangalore University, Mangalagangothri, Karnataka, 574199, India

    Prima Francis

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  1. Prima Francis
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PF and KC designed research, conducted experiments, and analyzed data. KC acquired funds and conceptualized the work. PF drafted the manuscript. KC reviewed and edited the manuscript. All authors read and approved the manuscript.

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Correspondence to Kajal Chakraborty.

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Francis, P., Chakraborty, K. Clathrolides A–B: previously undescribed macrocylic lactones from marine demosponge Clathria (Thalysias) vulpina (Lamarck, 1814) as potential antihypertensive leads attenuating angiotensin converting enzyme. Med Chem Res 30, 1438–1451 (2021). https://doi.org/10.1007/s00044-021-02743-4

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