Anti-inflammatory scalarane-type sesterterpenes, erectascalaranes A-B, from the marine sponge Hyrtios erectus attenuate pro-inflammatory cyclooxygenase-2 and 5-lipoxygenase

Chemical investigation of demosponge Hyrtios erectus (family Thorectidae) resulted in the identification of two scalarane-type sesterterpenes, erectascalaranes A-B, which were characterized as 3-((but-3(5)-enyloxy)methyl)-icosahydro-11-hydroxy-4,4,8,10,13-pentamethyl-20-oxochryseno[2,1-c]furan-12-yl acetate (erectascalarane A) and 3-((but-3(5)-enyloxy)methyl)-hexadecahydro-11-hydroxy-4,4,8,10,13-pentamethylchryseno[2,1-c]furan-20(5bH)-one (erectascalarane B) using detailed spectroscopic experiments. Erectascalarane A exhibited significantly greater attenuation property against pro-inflammatory cyclooxygenase-2 (IC50 0.80 mM) than that displayed by erectascalarane B (IC50 similar to 1 mM). Erectascalarane A was found to be a potential inhibitor against 5-lipoxygenase (IC50 1.21 mM), and its activity was significantly higher than that displayed by standard anti-inflammatory agent ibuprofen (IC50 4.50 mM, p < 0.05). Greater anti-inflammatory selectivity index of erectascalarane A (1.15) than ibuprofen (0.43) also accounted for greater selectivity of the former against cyclooxygenase-2. Erectascalarane A also exhibited significantly greater antioxidant activities against oxidants (IC50 similar to 0.8 mM) than the standard alpha-tocopherol (IC50 > 1.5 mM). Lesser docking parameters obtained for erectascalarane A at the active site of COX-2 and greater electronic factors acquired from structure-activity analyses (topological polar surface area 82.06) were also in agreement with greater anti-inflammatory activity. Lesser steric bulk and greater electronic properties combined with lower binding energy with cyclooxygenase-2 further reinforced the significant anti-inflammatory potential of erectascalarane A.