Fungal Secondary Metabolites: A Promising Source of Antineoplastic Drugs

Abstract

The rapid progress in understanding the molecular biology of cancer has made a large impact on the design and development of novel therapeutic strategies prompted by the multi-factorial limitations of the current chemotherapeutic modalities. Given that the development of newer antineoplastic drugs continues to rely heavily on isolation from natural sources rather than applications based on rational drug design and combinatorial chemistry, fungal secondary metabolites rank high on the list of potential targets for the discovery of novel chemotherapeutic agents. They represent a diverse group of bioactive compounds characterized by their origin and biosynthetic pathways. Also, they serve as regulators, chemical messengers in developmental processes, or as antibiotics. A broad variety of fungal secondary metabolites possess potent antitumor activity. Alpha sarcin, gliotoxins, trichodimerol, L-lysine alpha-oxidase, fumagillin, declauxin, chrysanthones, fungal-derived low molecular weight inhibitors of angiogenesis e.g. TNP-470, retamycin, daunorubicin, and doxorubicin all have been shown to exert potent antitumor activity. Inhibition of protein synthesis, induction of DNA breakage and apoptosis, as well as blockade of angiogenesis are examples of the multiple antitumor mechanisms of fungal secondary metabolites. The current review explores the potential use of fungal secondary metabolites as antineoplastic drugs with special reference to the novel hepatoma growth-inhibition factor that we recently characterized from Trichoderma viride.

Chemical investigations of endophytic and fungicolous fungi

“…112 Details of the isolation and structure elucidation of functionality at C-9. 2,4,5 The resonance for adjacent carbon C-10 was also shifted somewhat downfield relative to that of all other analogues lacking a heteroatom at C-9 (δ C 41.6 vs. ~ δ C 30). The remaining signals were assigned upon analysis of HMQC and HMBC data (Table 4.2).…”

“…Many other compounds with diverse bioactivities have been reported in the literature. [5][6][7] Fungi from a variety of ecological niches have been found to produce unique secondary metabolites. While some ecological niches have been extensively studied, many others are still underexplored.…”

“…4 Despite the negative reputation associated with such diseases, many fungi are also prolific sources of bioactive secondary metabolites. [5][6][7] Many antibiotic, 8 antifungal, 9 immunosuppresant, 10 and cholesterol-reducing agents 11 have been discovered from fungal sources. The "miracle drug" penicillin (1.1), is perhaps the most famous fungal antibiotic.…”

Chemical investigations of fungicolous and coprophilous fungi

“…To this end, there have been many studies focused on the discovery of natural products and synthetic agents active against A. flavus and C. albicans. [10][11][12] However, there are relatively few reports on studies that involve screening for antifungals effective against C. neoformans, and the treatment of CM remains challenging due to the limited number of anti-Cryptococcus agents that are currently available. 36 As such, current treatment protocols for CM involve the use of non-exclusive antifungal medications, sometimes accompanied by repeated clinical procedures such as lumbar punctures, and constant monitoring.…”

“…9 Fungi are also known to serve as productive sources of biologically active metabolites. [10][11][12] Many drugs with antifungal, antibiotic, immunosuppressive, and cholesterol-lowering properties have been discovered through chemical investigations of fungi. [13][14][15][16] The antifungal agent griseofulvin (1.1), originally isolated from Penicillium griseofulvum, has been in clinical use since the late 1960's and is on the World Health Organization's list of essential medicines.…”