Screening of ferulic acid related compounds as inhibitors of xanthine oxidase and cyclooxygenase-2 with anti-inflammatory activity

Nile, Shivraj Hariram; Ko, Eun Young; Kim, Doo Hwan; Keum, Young-Soo

doi:10.1016/j.bjp.2015.08.013

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Original Article • Rev. bras. farmacogn. 26 (1) • Jan-Feb 2016 • https://doi.org/10.1016/j.bjp.2015.08.013 copy

Screening of ferulic acid related compounds as inhibitors of xanthine oxidase and cyclooxygenase-2 with anti-inflammatory activity

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

The ferulic and gallic acid related compounds from natural origin were studied against xanthine oxidase and cyclooxygenase-2 along with their anti-inflammatory activity. The compounds gallic acid, ferulic acid, caffeic acid and p-coumaric acid revealed promising anti-inflammatory activity (30–40% TNF-α and 60–75% IL-6 inhibitory activity at 10 µM). Bioavailability of compounds were checked by in vitro cytotoxicity using CCK-8 cell lines and confirmed to be nontoxic, but found toxic at higher concentration (50 µM). Gallic, ferulic, caffeic acid was demonstrated potential dual inhibition toward xanthine oxidase and cyclooxygenase-2 as calculated by IC₅₀: 68, 70.2, and 65 µg/ml (xanthine oxidase) and 68.5, 65.2, and 62.5 µg/ml (cyclooxygenase-2), respectively. The structure activity relationship and in silico drug relevant properties (HBD, HBA, PSA, c Log P, ionization potential, molecular weight, E_HOMO and E_LUMO) further confirmed that the compounds were potential candidates for future drug discovery study, which was expected for further rational drug design against xanthine oxidase and cyclooxygenase.

Keywords
Ferulic acid; Gallic acid; Xanthine oxidase; Cyclooxygenase; SAR; Gout

Samples	% Inhibition at 10 µM
	TNF-α	IL-6	Toxicity
			10 µM	25 µM	50 µM
p -Coumaric acid	30	60	0	1.3	3.2
Ferulic acid	40	72	0	1.5	4
Caffeic acid	35	68	0	1.6	3.5
Sinapic acid	23	56	0	2.1	4.5
Alkyl ferulates	20	40	0	2.4	5
Gallic acid	48	75	0	1.6	3.5
Methyl gallate	16	30	0.4	3	8
Propyl gallate	18	35	0	2	5
Lauryl gallate	20	25	0.5	4	8
Stearyl gallate	15	20	0.4	2	7
Dexamethasone	60	92	0	0	3

Sample	Molecular formula	Molecular weight (g/mol)	Melting point (°C)	E _HOMO	E _LUMO	HBA	Mol. PSA	c Log P	Solubility	Drug likeness	Drug score
p -Coumaric acid	C₉H₈O₃	164	212	−4.28	−0.65	4	56.20	4.45	−4.20	0.53	0.32
Ferulic acid	C₁₀H₁₀O₄	194	170	−5.52	−0.61	5	56.20	4.12	−4.50	0.52	0.40
Caffeic acid	C₉H₈O₄	180	224	−4.25	−0.58	4	56.20	4.60	−4.20	0.41	0.38
Sinapic acid	C₁₁H₁₂O₅	224	204	−5.34	−0.70	4	65.5	5.40	−5.34	−0.22	0.35
Alkyl ferulates	C₄₀H₇₀O₄	614	96	−9.55	−0.85	6	85.5	6.86	−8.50	0.85	0.28
Gallic acid	C₇H₆O₅	170	260	−4.10	−0.60	4	55.40	4.11	−4.10	0.55	0.38
Methyl gallate	C₈H₈O₅	184	202	−4.61	−0.56	4	55.20	4.20	−4.22	−0.32	0.30
Propyl gallate	C₁₀H₁₂O₅	212	150	−5.45	−0.55	5	60.5	5.10	−4.40	−0.23	0.25
Lauryl gallate	C₁₉H₃₀O₅	338	98	−6.28	−0.68	5	72.5	6.85	−5.30	−0.42	0.22
Stearyl gallate	C₂₅H₄₂O₅	423	105	−6.85	−0.75	6	75.5	6.20	−6.10	−0.65	0.20

Sociedade Brasileira de Farmacognosia Universidade Federal do Paraná, Laboratório de Farmacognosia, Rua Pref. Lothario Meissner, 632 - Jd. Botânico, 80210-170, Curitiba, PR, Brasil, Tel/FAX (41) 3360-4062 - Curitiba - PR - Brazil
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[1] * Corresponding author. rational@konkuk.ac.kr