Department of Biology, Biogen Laboratory, Universidade Federal de Lavras (UFLA), Lavras, Brazil.
Department of Chemistry, Biochemistry Laboratory, Universidade Federal de Lavras (UFLA), Lavras, Brazil.
Lett Appl Microbiol. 2019 Aug;69(2):88-95. doi: 10.1111/lam.13171. Epub 2019 Jul 1.
Natural enzyme inhibitors have been widely described in literature because of its pharmacological and cosmetic applications. Fungi found in caves represent a promising source of bioactive substances that are still little explored scientifically. Thus, the present work evaluated the presence of enzymatic modulators in a filtrate obtained from the cultivation of the cave fungus Lecanicillium aphanocladii (Family: Cordycipitaceae). Snake venoms from Bothrops alternatus and Bothrops atrox were used as an enzymatic source for the induction of the phospholipase, proteolytic, thrombolytic, cytotoxic and coagulant activities. Compounds present in the fungal filtrate inhibited 50, 23·8, 26·6, 50·9 and 52·5% of the proteolytic, phospholipase, haemolytic, thrombolytic and coagulant activities respectively. The filtrate was not cytotoxic on erythrocytes, but induced partial dissolution of thrombi. Fungal enzyme inhibitors that have low or no toxicity and can be obtained on a large scale and at low cost are relevant in the medical-scientific context. Therefore, the inhibition of phospholipases A and proteases observed in the present work highlights the potential of fungal metabolites for the development of drugs that can be used in the treatment of haemostasis and inflammation-related disorders. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, secondary metabolites synthesized by Lecanicillium aphanocladii, a fungus isolated from caves, demonstrated modulating action on proteases and phospholipases A present in snake venoms of the Bothrops genus, widely used as tools for the study of pathophysiology processes related to haemostasis and inflammation. The results suggest the possibility of future applications for these metabolites in the development of pharmaceuticals of medical-scientific interest.
天然酶抑制剂因其在药理学和化妆品方面的应用而在文献中被广泛描述。洞穴中发现的真菌是具有生物活性物质的有前途的来源，但目前科学上对其仍知之甚少。因此，本研究评估了从洞穴真菌蜡蚧轮枝菌（属：虫草科）培养物中获得的滤液中是否存在酶调节剂。使用矛头蝮蛇和矛头蝮蛇的蛇毒作为诱导磷脂酶、蛋白水解酶、溶栓酶、细胞毒性和凝血酶活性的酶源。真菌滤液中的化合物分别抑制了 50%、23.8%、26.6%、50.9%和 52.5%的蛋白水解酶、磷脂酶、溶血酶、溶栓酶和凝血酶活性。该滤液对红细胞无细胞毒性，但能诱导部分血栓溶解。在医学科学背景下，具有低毒性或无毒性、可大规模获得且成本低廉的真菌酶抑制剂具有重要意义。因此，本研究中观察到的对磷脂酶 A 和蛋白酶的抑制作用突出了真菌代谢物在开发可用于治疗止血和炎症相关疾病的药物方面的潜力。
