Fungal Metabolite Antagonists of Plant Pests and Human Pathogens: Structure-Activity Relationship Studies

Abstract

Fungi are able to produce many bioactive secondary metabolites that belong to different classes of natural compounds. Some of these compounds have been selected for their antagonism against pests and human pathogens and structure-activity relationship (SAR) studies have been performed to better understand which structural features are essential for the biological activity. In some cases, these studies allowed for the obtaining of hemisynthetic derivatives with increased selectivity and stability in respect to the natural products as well as reduced toxicity in view of their potential practical applications. This review deals with the SAR studies performed on fungal metabolites with potential fungicidal, bactericidal, insecticidal, and herbicidal activities from 1990 to the present (beginning of 2018).

Keywords: SAR studies; bactericides; bioactive natural products; fungal secondary metabolites; fungicides; herbicides; insecticides.

Figure 1

The structures of sphaeropsidins A–F (1–6) and sphaeropsidones (7 and 8) and their chlorinated analogs (9 and 10).

Scheme 1

The structures of sphaeropsidin A (1) and its derivatives (2, 11–14).

Scheme 2

The structures of sphaeropsidin B (2) and its derivative (15).

Scheme 3

The structures of sphaeropsidin C (3) and its derivatives (16–18).

Scheme 4

The structures of sphaeropsidone (7) and its derivatives (19–24).

Scheme 5

The structures of epi-sphaeropsidone (8) and its derivatives (25 and 26).

Figure 2

The structures of afritoxinones A and B (27 and 28), oxysporone (29), R-(−)-mellein, (3R,4R)-4-hydroxymellein, and (3R,4S)-4-hydroxymellein (30–32).

Scheme 6

The structures of oxysporone (29) and its derivatives (33–40).

Figure 3

The structures of ascochalasin (41); deoxaphomin (42); cytochalasin A (43); cytochalasin B (44); 7,20-O,O′-diacetylcytochalasin B (45); 21,22-dihydrocytochalasin B (46); 17-O-acetylcytochalasin A (47); and cytochalasins C, D, E, H, and J (48–52, respectively).

Figure 4

The structures of 12β-hydroxy-13α-methoxyverruculogen TR-2 (53); 3-hydroxyfumiquinazoline A (54); fumitremorgin C (55); cyclotryprostatins A (56) and B (57); verruculogen TR-2 (58); 12β-hydroxyverruculogen TR-2 (59); fumitremorgin B (60); verruculogen (61); and fumiquinazolines F, G, D, and A (62−65).

Figure 5

The structures of fusapyrone (66), its derivatives (68,70–75), deoxyfusapyrone (67), and its derivative (69).

Figure 6

The structures of 6-n-pentyl-2H-pyran-2-one and viridepyronone (76 and 77).

Scheme 7

The structures of fusaproliferin (78) and its derivatives (80–83).

Scheme 8

The structures of terpestacin (79) and its derivatives (84–87).

Scheme 9

The structures of sphaeropsidin A (1) and its derivatives (88–91).

Scheme 10

The structures of sphaeropsidin B (2) and its derivatives (92–94).

Figure 7

The structures of fischerindoline (95), eurochevalierine (96), neosartins A–C (97–99), 1,2,3,4-tetrahydro-2,3-dimethyl-1,4-dioxopyrazino[1–a]indole (100), 1,2,3,4-tetrahydro-2-methyl- 3-methylene-1,4-dioxopyrazino[1–a]indole (101), 1,2,3,4-tetrahydro-2-methyl-1,3,4-trioxopyrazino [1–a]indole (102), N-methyl-1H-indole-2-carboxamide (103), gliotoxin (104), acetylgliotoxin (105), reduced gliotoxin (106), 6-acetylbis(methylthio)gliotoxin (107), bisdethiobis(methylthio)gliotoxin (108), didehydrobisdethiobis(methylthio)gliotoxin (109), bis-N-norgliovictin (110), and pyripyropene A (111).

Figure 8

The structures of boydines A–D (112–115).

Figure 9

The structures of 4a-epi-9α-methoxydihydrodeoxybostrycin (116), 10-deoxybostrycin (117), nigrosporin B (118), 9α-hydroxydihydrodesoxybostrycin (119), 9α-hydroxyhalorosellinia A (120), 4-deoxybostrycin (121), bostrycin (122), austrocortirubin (123), 3,5,8-trihydroxy-7-methoxy-2-methylanthracene-9,10-dione (124), 3-acetoxy-4-deoxybostrycin (125), 3-acetoxybostrycin (126), 8-acetoxy-3,5-dihydroxy-7-methoxy-2-methylanthracene-9,10-dione (127), 5-acetoxy-3,8-dihydroxy-7-methoxy-2-methylanthracene-9,10-dione (128), 3-acetoxy-5,8-dihydroxy-7-methoxy-2-methylanthracene-9,10-dione (129), 5,8-diacetoxy-3-hydroxy-7-methoxy-2-methylanthracene-9,10-dione (130), 3,8-diacetoxy-5-hydroxy-7-methoxy-2-methylanthracene-9,10-dione (131), 3,5-diacetoxy-8-hydroxy-7-methoxy-2-methylanthracene-9,10-dione (132), 3,5,8-triacetoxy-7-methoxy-2-methylanthracene-9,10-dione (133), and 8-acetoxyaustrocortirubin (134).

Figure 10

The structures of spiromastixones A–O (135−149).

Scheme 11

The structures of cyclopaldic acid (150) and its derivatives (151–159).

Scheme 12

The structures of seiridin (160), its derivatives (161–163), and isoseiridin (164).

Scheme 13

The structures of sphaeropsidins A and B (1 and 2) and their derivatives (165 and 166).

Figure 11

The structures of papyracillic acid (167) and some of its derivatives (168–178).

Figure 12

The structures of preaustinoid A (179), preaustinoid B (180), preaustinoid A2 (181), dehydroaustin (182), acetoxydehydroaustin (183), neoaustin (184), and austin (185).

Figure 13

The structures of okaramines A, B, C, G, H, I, N, and Q (186–193); 2-Dehydroxy-3-demethoxy okaramine B (194); and cyclo(N⁸-(α,α-dimethylallyl)-L-Trp-6a′-(α,α-dimethylallyl)-L-Trp) (195).

Figure 14

The structures of chenopodolin (196); stagonolide (197); putaminoxin (198); pinolidoxin (199); cytochalasins F, T, Z1, Z2, and Z3 (200–204); agropyrenol (205); and phomentrioloxin (206).

Figure 15

The structures of fusicoccin A (207), dideacetylfusicoccin A (208), the isopropylidene derivative of fusicoccin aglycone (209), and the hexacetyl and pentacetyl isomers of 16-O-demethyl-de-tert-pentenylfusicoccin A (210 and 211).

Scheme 14

The structures of sphaeropsidone (7), its derivatives (212 and 213), epi-sphaeropsidone (8), and its derivatives (214 and 215).

Figure 16

The structures of cochliotoxin (216), radicinin (217), 3-epi-radicinin (218), radicinol (219), 3-epi-radicinol (220), chloromonilinic acids B–D (221–223), and chloromonilicin (224).