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Abstract：
Metabolites exploration of the ethyl acetate extract of Fusarium solani culture broth that was isolated from Euphorbia tirucalli root afforded five compounds; 4-hydroxybenzaldehyde (1), 4-hydroxybenzoic acid (2), tyrosol (3), azelaic acid (4), malic acid (5), and fusaric acid (6). Fungal extract as well as its metabolites were evaluated for their anti-inflammatory and anti-hyperpigmentation potential via in vitro cyclooxygenases and tyrosinase inhibition assays, respectively. Azelaic acid (4) exhibited powerful and selective COX-2 inhibition followed by fusaric acid (6) with IC50 values (2.21 ± 0.06 and 4.81 ± 0.14 μM, respectively). As well, azelaic acid (4) had the most impressive tyrosinase inhibitory effect with IC50 value of 8.75 ± 0.18 μM compared to kojic acid (IC50 = 9.27 ± 0.19 μM). Exclusive computational studies of azelaic acid and fusaric acid with COX-2 were in good accord with the in vitro results. Interestingly, this is the first time to investigate and report the potential of compounds 3-6 to inhibit cyclooxygenase enzymes. One of the most invasive forms of skin cancer is melanoma, a molecular docking study using a set of enzymes related to melanoma suggested pirin to be therapeutic target for azelaic acid and fusaric acid as a plausible mechanism for their anti-melanoma activity.
摘要：
从一品红根中分离出的镰刀菌培养液的乙酸乙酯提取物的代谢物探索提供了五种化合物；4-羟基苯甲醛（1），4-羟基苯甲酸(2),酪醇（3），壬二酸（4），苹果酸（5），和镰刀酸（6）。通过体外环氧合酶和酪氨酸酶抑制试验，评估了真菌提取物及其代谢物的抗炎和抗色素沉着潜能，分别。壬二酸（4）表现出强大和选择性的COX-2抑制作用，其次是镰刀酸（6），IC50值（2.21±0.06和4.81±0.14μM，分别)。同样,与曲酸相比，壬二酸（4）具有最令人印象深刻的酪氨酸酶抑制作用，IC50值为8.75±0.18μM（IC50=9.27±0.19μM）。用COX-2对壬二酸和褐煤酸进行的独家计算研究与体外结果吻合良好。有趣的是,这是首次研究和报道化合物3-6抑制环氧合酶的潜力。最具侵袭性的皮肤癌之一是黑色素瘤，一项使用一组与黑色素瘤相关的酶的分子对接研究表明，pirin是壬二酸和镰刀酸的治疗靶标，这是它们抗黑色素瘤活性的合理机制。
