Anti-inflammatory pregnane-type steroid derivatives clathroids A-B from the marine Microcionidae sponge Clathria (Thalysias) vulpina: Prospective duel inhibitors of pro-inflammatory cyclooxygenase-2 and 5-lipoxygenase

Francis, Prima and Chakraborty, Kajal (2021) Anti-inflammatory pregnane-type steroid derivatives clathroids A-B from the marine Microcionidae sponge Clathria (Thalysias) vulpina: Prospective duel inhibitors of pro-inflammatory cyclooxygenase-2 and 5-lipoxygenase. Steroids, 172. pp. 1-9.

[img] Text
Steroids_2021_Kajal Chakraborty_Anti-inflammatory pregnane-type steroid derivatives clathroids A-B.pdf
Restricted to Registered users only

Download (4MB) | Request a copy | Please mail the copy request to cmfrilibrary@gmail.com
Official URL: https://www.sciencedirect.com/science/article/pii/...
Related URLs:

    Abstract

    Two pregnane-type of steroid derivatives characterized as 5α-pregna-3β-methyl pent-3-enoate-12β, 16β diol-20-one (clathroid A) and 12β,15β- dihydroxypregna-4,6-diene-3,20-dione (clathroid B) were purified from the crude extract of the marine sponge, Clathria (Thalysias) vulpina (family Microcionidae) by extensive chromatographic fractionation. Spectroscopic methods including nuclear magnetic resonance spectroscopy were employed to characterize the purified clathroids A-B. The studied compounds exhibited duel inhibitory potentials against pro-inflammatory cyclooxygenase-2 and 5-lipoxygenase (median inhibitory concentration, IC50 < 1 mM), whereas the attenuation property of clathroid A against 5-lipoxygenase (IC50 0.85 mM) was greater than the standard anti-inflammatory ibuprofen (IC50 4.51 mM, p < 0.05). Greater selectivity index (anti cyclooxygense-2/anti cyclooxygense-1) of the studied clathroids (>1) than ibuprofen (0.43) attributed the greater selective attenuation properties towards pro-inflammatory inducible cyclooxygenase-2 than its constitutive isoenzyme cyclooxygenase-1. The antioxidant potentials of clathroid A against 2, 2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (IC50 0.80 mM) and diphenyl-1-picrylhydrazyl (IC50 0.83 mM) free radicals were greater than those of clathroid B (IC50 0.86–0.96 mM). Structure–activity analyses showed that the bioactivities of the clathroids were directly related to their electronic parameters coupled with permissible hydrophobic properties. Clathroid A exhibited grater electronic parameter (topological polar surface area tPSA, 83.83) than clathroid B (74.60) and ibuprofen (37.30), which were found to be in agreement with the prospective anti-inflammatory profile of clathroid A. Clathroid A exhibited higher number of hydrogen bonding interactions with 5-lipoxygenase active site and lesser docking values, such as docking score (DS −12.90 kcal mol−1) and inhibition constant (Ki 1.11 nM) than those recorded by clathroid B (DS −10.49 kcal mol−1; Ki 13.88 nM). The molecular binding properties of clathroid A with 5-lipoxidase inferred that its docking score/ binding energy were positively correlated with their in vitro bioactivie potentilas. A putative biosynthetic pathway of the studied clathroids was proposed from a pregnenolone precursor. The present study recognized the potential of clathroid A isolated from C. (Thalysias) vulpina as prospective anti-inflammatory lead that could find its use in medicinal applications.

    Item Type: Article
    Uncontrolled Keywords: Clathria (Thalysias) vulpina; Microcionidae Clathroids A-B; Pregnane-type steroid derivatives; Anti-inflammatory activity; Cyclooxygenase-2 and 5-lipoxygenase
    Subjects: Fish Biotechnology > Bioactive compound
    Marine Ecosystems > Sponges
    Fish Biotechnology
    Divisions: CMFRI-Kochi > Marine Biotechnology
    Subject Area > CMFRI > CMFRI-Kochi > Marine Biotechnology
    CMFRI-Kochi > Marine Biotechnology
    Subject Area > CMFRI-Kochi > Marine Biotechnology
    Depositing User: Arun Surendran
    Date Deposited: 21 Jun 2021 05:59
    Last Modified: 21 Jun 2021 05:59
    URI: http://eprints.cmfri.org.in/id/eprint/15147

    Actions (login required)

    View Item View Item