RESUMEN
Chromene derivatives with manifold structural framework and pharmacological properties were ubiquitous in the mollusks of marine origin. A previously undescribed 1H-benzochromenone was isolated through bioassay-guided chromatographic purification of the organic extract of the marine gastropod mollusk Chicoreus ramosus. The compound was characterised as 6-(2',2'-dimethyl)-3'-en-1'-yl-1'-oxy)-3-hydroxy-1H-benzo[c]chromene-2(10aH)-one based on integrated spectroscopic analysis. The antioxidant studies by employing the stable free radicals reported that the antioxidant activity (IC50 1.4-1.6 mM) was comparable to α-tocopherol (IC50 1.4-1.7 mM). The attenuating potential of the studied compound against pro-inflammatory 5-lipoxygenase (IC50 2.12 mM) was significantly greater than that exhibited by anti-inflammatory drug ibuprofen (IC50 4.4 mM), whereas its inhibitory properties against carbolytic α-amylase (IC50 â¼0.72 mM) was comparable with that displayed by acarbose (IC50 0.43 mM). The present study recognised the potential of 1H-benzochromenone derivative isolated from C. ramosus as important pharmaceutical lead with anti-diabetic and anti-inflammatory potentials to reduce the risk of hyperglycaemia and inflammatory pathologies.
Asunto(s)
Antiinflamatorios/farmacología , Antioxidantes/farmacología , Inhibidores Enzimáticos/farmacología , Gastrópodos/química , Animales , Antiinflamatorios/química , Araquidonato 5-Lipooxigenasa/metabolismo , Benzopiranos/química , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/química , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Inhibidores de la Lipooxigenasa/química , Inhibidores de la Lipooxigenasa/farmacología , Estructura Molecular , alfa-Amilasas/antagonistas & inhibidoresRESUMEN
Three macrolides bearing the carbon framework of oxabicyclo[21.3.1]heptacosa-ene-diones (A and B) and oxabicyclo[19.3.1]pentacosa-ene-dione (C) were isolated and characterised from the organic extract of the intertidal red seaweed Gracilaria salicornia (family Gracilariaceae), which were named as salicornolides A-C. These natural macrolides were conformationally pre-organised ring structure providing diverse functionalities, and their potential bioactive properties led to the development of pharmacophores with anti-inflammatory properties. The 21-membered pyran-enclosed salicornolide B displayed greater cyclooxygenase-2 (IC50 COX-2 1.13 mM) inhibitory activity than those exhibited by the 21-membered aryl salicornolide A and 19-membered salicornolide C (IC50 COX-2-1.2 mM). The attenuating potential of the studied compounds against pro-inflammatory enzyme, 5-lipoxygenase (IC50 LOX < 1.5 mM) was significantly greater than that displayed by the non-steroidal anti-inflammatory ibuprofen (IC50 4.5 mM), whereas the selectivity indices exhibited by salicornolides against cyclooxygenase-2 was significantly higher (1.18-1.41, P < 0.05) when compared to that of ibuprofen (SI 0.43) attributing the greater selectivity profile of the former towards inducible pro-inflammatory mediators than the latter. The minimal binding energy of salicornolide B (-9.64 kcal mol-1), a greater number of hydrogen-bonds and lesser inhibitory constant (Ki 85.15 nM) might be responsible for effective binding towards 5-lipoxygenase, and that could attribute its greater anti-inflammation potential than those displayed by other compounds. The putative biosynthetic cascade initiated by malonate-acyl carrier protein unambiguously confirmed the structural attributions of the titled macrocyclic lactones. The undescribed salicornolides A-C from seaweed Gracilaria salicornia attenuating pro-inflammatory 5-lipoxygense might be considered as prospective natural anti-inflammatory leads for pharmaceutical applications.
Asunto(s)
Chenopodiaceae , Gracilaria , Antiinflamatorios , Antiinflamatorios no Esteroideos , Antioxidantes , Ciclooxigenasa 2 , Inhibidores de la Lipooxigenasa , Estudios ProspectivosRESUMEN
The muricid gastropod, Chicoreus ramosus, is a nutrient-enriched food source available along the coastal peninsular of the Indian subcontinent. This study was aimed at bioactivity-directed chromatographic fractionation of the organic extract of C. ramosus to isolate an unprecedented drimane-type sesquiterpenoid Ramosane, characterized as 3-hydroxy-7,9b-dimethyl-5-methylene-8-pentyl-octahydro-1H-cyclopenta[a]naphthalen-9(2H)-one. The compound possessed potential antioxidant activities {2, 2'-diphenyl-1-picryl hydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activities of IC50 1.42 mM and 1.72 mM, respectively} and was proportionate with those (IC50 1.39 and 1.69 mM, respectively) exhibited by α-tocopherol. The studied sesquiterpenoid exhibited potential attenuation property countering the pro-inflammatory 5-lipoxygenase (IC50 ~ 4 mM), and its activity was analogous with that exhibited by the anti-inflammatory ibuprofen (IC50 4.36 mM), whereas its carbolytic α-amylase activity (IC50 0.96 mM) was commensurate with that displayed by acarbose (IC50 0.43 mM). The isolated metabolite might anticipate as potential naturally derived bioactive constituent in functional food and pharmaceutical applications. PRACTICAL APPLICATIONS: The edible marine muricid gastropod C. ramosus is a prominently available gastropod species of commercial significance in the coastal regions of Indian Peninsula. An unprecedented drimane-type sesquiterpenoid Ramosane was isolated through the bioactivity-directed chromatographic fractionation of the organic extract of muricidae C. ramosus displaying potential anti-inflammatory and anti-diabetic properties. The present study apprehended the prospective of drimane-type sesquiterpenoid derivative Ramosane purified from C. ramosus as a naturally derived pharmacophore with anti-diabetic and anti-inflammatory potential for utilization in functional food and pharmaceutical formulations to minimize the likelihood of inflammation and hyperglycemic pathologies.
Asunto(s)
Antiinflamatorios/farmacología , Antioxidantes/farmacología , Gastrópodos/química , Inhibidores de la Lipooxigenasa/farmacología , Sesquiterpenos Policíclicos/farmacología , Sesquiterpenos/farmacología , Animales , Antiinflamatorios/química , Antioxidantes/química , Araquidonato 5-Lipooxigenasa/metabolismo , Inhibidores de la Lipooxigenasa/química , Sesquiterpenos Policíclicos/química , Sesquiterpenos/químicaRESUMEN
The Asian green mussel, Perna viridis is a nutritious health food in the estuarine and coastal sea beds of the Arabian Sea along the west coast of India. In the present study, bioactivity-guided purification of the chloroform fraction of the methanolic extract of P. viridis was carried out. The isolated secondary metabolites were characterized by spectroscopic experiments, and their antioxidative/antiinflammatory properties were evaluated. The titled compounds were characterized as 3-hydroxy-13-vinyl-dodecahydro-11-phenanthrenone (1), 4,4,9-trimethyl-13-vinyl-dodecahydro-2-phenanthrenone (2), 11,20-dihydroxy-6,6-dimethyl-decahydro-5H-benzo[h]naphtho[1,2-c]chromene-16-carbaldehyde (3), 16-acetyl-20-hydroxy-6,6-dimethyl-dodecahydro-5H-benzo[h]naphtho[1,2-c]chromen-12-one (4), cholest-5-en-3ß-3-yl-(30-hydroxy-3-methyl-36-methyleneundeca-30E,34E-dienoate) (5), and cholest-5-en-3ß-3-yl-((E)-33-oxooct-31-enoate) (6). No significant differences in the antioxidant activities of the compounds with chromene-16-carbaldehyde (3) and chromen-12-one (4) functionalities (IC50 0.52-0.68 mg/ml) vis-à-vis the positive control, α-tocopherol (IC50 0.65-0.76 mg/ml) were registered. The studied compounds, 1-4, displayed potential antiinflammatory activities against pro-inflammatory 5-lipoxygenase (5-LOX) (IC50 < 1 mg/ml). The balanced hydrophilic-lipophilic properties and lower steric values of the studied compounds, 1-4, were correlated with their bioactive potentials. PRACTICAL APPLICATIONS: The edible bivalve green mussels, P. viridis, are broadly available in the estuarine and coastal regions of the Indian Peninsula. The sequential chromatographic purification of the chloroform fraction of the methanolic extract of P. viridis led to the identification of six pure secondary metabolites. The metabolites with substituted chromene-16-carbaldehyde and chromen-12-one functionalities displayed potential antioxidative and antiinflammatory activities compared to other studied compounds. These bioactive metabolites could be used in functional food formulations and as antioxidant leads in medicinal food applications.