Fruitful Decade of Fungal Metabolites As Anti-Diabetic Agents from 2010 to 2019: Emphasis on A-Glucosidase Inhibitors
Total Page：16
File Type：pdf, Size：1020Kb
Phytochem Rev (2021) 20:145–179 https://doi.org/10.1007/s11101-020-09733-1 (0123456789().,-volV)( 0123456789().,-volV) Fruitful decade of fungal metabolites as anti-diabetic agents from 2010 to 2019: emphasis on a-glucosidase inhibitors Hidayat Hussain . Mamona Nazir . Muhammad Saleem . Ahmed Al-Harrasi . Elizbit . Ivan R. Green Published online: 5 February 2021 Ó The Author(s) 2021 Abstract In recent years the prevalence of diabetes Keywords Fungi Á Secondary metabolites Á a- has increased globally and by 2040 the number of Glucosidase Á Anti-diabetic diabetic people has been estimated to increase to 642 million. Various classes of drugs are available to treat Type ll diabetes. However, these drugs are associated with certain side effects. a-Glucosidase is an intri- Introduction quing target enzyme to treat Type II diabetes, and a- glucosidase inhibitors are considered as first-line Diabetes mellitus (DM) is a metabolic disorder drugs for Type ll patients. Fungi, in general, produce associated with insulin resistance and the inability of natural products with some amazing chemical diver- the pancreatic b-cells to produce insulin, which leads sity and many fungal metabolites have illustrated a to hyperglycemia. Moreover, hyperglycemia is asso- wide range of biological and pharmacological effects. ciated with polyuria, weight loss, ketoacidosis, poly- In this review the focus is on describing the a- dipsia, and other life-threatening health conditions glucosidase effects and their potential as anti-diabetic (Usman et al. 2019). AGIs are an intriguing class of agents of various metabolites isolated from fungi. pharmaceutical drugs most often considered as first- line antidiabetic drugs for Type ll patients (Hossain and Pervin 2018; Usman et al. 2019). However, in H. Hussain (&) A. Al-Harrasi Department of Bioorganic Chemistry, Leibniz Institute of Natural and Medical Sciences Research Center, Plant Biochemistry, Weinberg 3, 06120 Halle (Saale), University of Nizwa, Nizwa 616, Sultanate of Oman Germany e-mail: [email protected] Elizbit Department Materials Engineering, National University of M. Nazir Sciences and Technology (NUST) H12, Islamabad, Department of Chemistry, Government Sadiq College Pakistan Women University Bahawalpur, Bahawalpur 63100, Pakistan I. R. Green Department of Chemistry and Polymer Science, M. Saleem (&) University of Stellenbosch, Department of Chemistry, Baghdad Campus, The Islamia Private Bag X1, Matieland, Stellenbosch 7600, South University of Bahawalpur, Bahawalpur 63100, Pakistan Africa e-mail: [email protected] 123 146 Phytochem Rev (2021) 20:145–179 some studies, it has been reported that AGIs can be AGIs, and this has restricted their clinical usage (Yin employed as second-line antidiabetic drugs if these et al. 2014; Kao et al. 2016; Usman et al. 2019). inhibitors are used as combination therapy with Therefore, there is a crucial need to discover and metformin (Chan et al. 2018). develop new and safer anti-diabetic drugs with low The a-glucosidase enzyme (EC 3.2.1.20) has been toxicity. Natural products for this purpose would be considered as an important therapeutic target to treat ideal if they could combat such diseases without carbohydrate mediated illnesses. It is well known that creating other secondary health issues. Plant sec- the secretion of a-glucosidase occurs in the small ondary metabolites have especially been widely intestine and this enzyme catalyzes the cleavage of studied for their potential anti-diabetic properties. It disaccharides and oligosaccharides into monosaccha- is thus conceivable that diverse compounds derived rides in the final step of carbohydrate digestion. from fungal sources could be developed or trans- Moreover, the conversion of complex carbohydrates formed into new therapeutics against diabetes. This into monosaccharides enhances the glucose body level review article describes some small molecules isolated (Abbas et al. 2019). Numerous studies have demon- in the last decade (2010 to 2019) from various fungi strated that a-glucosidase inhibitors slow down the and developed as inhibitors of a-glucosidase, and thus absorption and digestion of carbohydrates and there- represent potential anti-diabetic drug leads. fore reduce the postprandial blood glucose concentra- tions which thus require less demand for insulin. a- Glucosidase inhibitors are considered mild compared Alkaloids to other oral antihyperglycemic agents because of their confined operation in the intestine rather than regu- Alkaloids are nitrogen containing natural products and lating various complex biochemical operations within have been recognized substances in the treatment of the body (Abbas et al. 2019). human diseases for many years (Pervaiz et al. 2016; Fungi are considered one of the richest sources of Rehman and Khan 2016). Literature indicated that a natural products among living organisms because significant number of alkaloids from plant sources fungi have a unique metabolic system and can have been identified as a-glucosidase inhibitors (Yin synthesise various types of natural products with quite et al. 2014). On the other hand, a number of alkaloids intriquing chemical diversity (Srivastava 2019). After have been reported from various fungi possessing a the discovery of penicillin (penicillin F) in 1929 by diverse range of biological effects (Mahmood et al. Alexander Fleming, substantial research on fungi lead 2010). Some alkaloids have also been reported from to the isolation of thousands of new fungal metabolites various fungi, which illustrated a-glucosidase inhibi- with a diverse range of biological and pharmacolog- tion. Valle et al. reported that benzomalvin A (1), ical effects (Srivastava 2019). Besides, penicillins quinolactacins A1 (2), A2 (3) in a mixture between B (antibacterial), echinocandin B (antifungal), cyclos- (4) and asperphenamate (5) (Fig. 1) were produced porin A (immunosuppressive, and lovastatin (choles- from the fungus Penicillium spathulatum (Valle et al. terol-lowering) are all fungal originated and marketed 2016). pharmaceutical drugs. Furthermore, these factors Moreover, the crude extract of P. spathulatum evidently illustrate the significance of fungal metabo- displays a-glucosidase effects with IC50: 56.5 lg/mL. lites to be a sustainable resource for new pharmaceu- Indeed, compounds 1 (IC50: 383.2 lg/mL), the mix- tical agents. ture of 2 and 3 (IC50: 273.3 lg/mL), 4 (IC50: 57.3 lg/ Currently, acarbose and miglitol are two commer- mL), and 5 (IC50: 8.3 lg/mL) display a reasonable cially available drugs with activity described as a- degree of a-glucosidase inhibition (Table 1). With an glucosidase inhibitors (AGIs). These pharmaceutical in vivo oral sucrose tolerance evaluation; compound 1 drugs furthermore inhibit the absorption of carbohy- was also tested in normal and hyperglycemic mice drates from the gut and thus these anti-diabetic drugs (p \ 0.05). Further docking studies revealed a higher are either administered alone or in combination with binding affinity of 1 to yeast and mammalian a- insulin (Bhatia et al. 2019; Hung et al. 2012). glucosidase and this activity has been reported as even However, serious gastrointestinal damage and liver higher than that of acarbose. The formalin assay injuries have been associated with the use of these studies substantiated antihyperalgesic activity 123 Phytochem Rev (2021) 20:145–179 147 Fig. 1 Structures of alkaloids 1–5 (p \ 0.05) of compound 1 in hyperglycemic mice (alkaloid 8). On the other hand, various alky sub- (Valle et al. 2016). Benzomalvin A (1) was also stituents attached to the nitrogen dramatically previously reported from the fungus Penicillium sp decreased activities (Wang et al. 2014). Penicidone (Sun et al. 1994), quinolactacins A1 (2), A2 (3) from C(12) was reported from Penicillium sp. (He et al. the fungus Xylariaceae sp (Nong et al. 2014), and 2019; Ge et al. 2008) and demonstrated a-glucosidase quinolactacin B (4) from the fungus Penicillium sp. inhibition with a low IC50: 51.9 lM (He et al. 2019). (Takahashi et al. 2000; Kakinuma et al. 2000). On the other hand, asperphenamate (5) was reported as a fungal metabolite from Penicillium sp. (Frisvad et al. Azaphilones 2013; Arai et al. 2017) and the fungus Aspergillus versicolor (Hou et al. 2017) as well as a plant Most of the azaphilones have been reported from two metabolite reported from Antidesma ghaesembilla fungi families viz., Xylariaceae and Trichocomaceae (Schaefer et al. 2017) and Erythrina droogmansiana and most of these compounds were reported from the (Yaya et al. 2014). fungal genera viz., Chaetomium, Penicillium, Mon- Isoindolinone type alkaloids, viz., the sterenins A-C ascus and Talaromyces. The azaphilones illustrated (6–8) (Ito-Kobayashi et al. 2008; Wang et al. 2014) interesting pharmacological effects viz., anti-fungal, and K-M (9–11) Wang et al. 2014) (Fig. 2) were antimicrobial, antioxidant, antiviral, anti-inflamma- reported from the fungus Stereum sp. and tested for tory, cytotoxic, and nematicidaland activities (Osman- their potential as a-glucosidase inhibitors. The chem- ova et al. 2010; Gao et al. 2013). Talaraculones A (13) ical diversity generated among these alkaloids is and B (14) (Fig. 3) were reported from the fungus mainly due to the different substituent groups on Talaromyces aculeatus and compounds 13 and 14 nitrogen (Wang et al. 2014). These compounds illustrated a-glucosidase potential with IC50: 78.6 and possess a-glucosidase effects with IC50: 3.31 to 22.9 lM, respectively, which are lower than