Characterization and Antifungal Activity of Limonoid Constituents Isolated from Meliaceae Plants Melia dubia, Aphanamixis polystachya, and Swietenia macrophylla against Plant Pathogenic Fungi In Vitro

School of Chemistry Biology and Environment, Vinh University, Vinh, Nghean 43100, Vietnam School of Natural Sciences Education, Vinh University, Vinh, Nghean 43100, Vietnam R&D Center of Bioactive Compounds, Vietnam Institute of Industrial Chemistry, Hanoi 10000, Vietnam Ho Chi Minh City University of Natural Resources and Environment, Ho Chi Minh 72114, Vietnam *e School of Chemical Engineering, Hanoi University of Science and Technology, Hanoi 10000, Vietnam Institute of Biotechnology and Food Technology, Industrial University of Ho Chi Minh City, Ho Chi Minh 71408, Vietnam Hanoi National University of Education, Hanoi 10000, Vietnam


Introduction
e Meliaceae family has 50 genera and 1,400 species and distributed in tropical and subtropical regions as the Americas, west India, Southeast Asia, and Southern China [1,2]. Almost all limonoids (more than 300 compounds) have been identified, and about one-third has been found in Azadirachta indica and Melia azedarach [3].
ere were more than 160 limonoids isolated from four species of the genus Swietenia [4]. e seeds of S. macrophylla contain bioactive compounds with anti-inflammatory, antimutagenicity, and antitumor activity, which has been used in traditional medicine in the world. Furthermore, the seeds of S. macrophylla in Malaysia are used traditionally to treat hypertension, diabetes, and relieve pain [1]. Limonoids and their derivatives are determined as the major constituents of S. macrophylla. e application of limonoids in plant protection has been developed since the 1960s. To date, most of the Meliaceous limonoids have been reported to be related to antifeedant, insecticidal, cytotoxic, antimalarial, and anticancer activity. Azadirachtin is an insect growth regulator and feeding deterrent that affects more than 60 insects such as aphids, caterpillars, leafhoppers, leafminers, mealybugs, psyllids, thrips, and whiteflies by effects on feeding and reducing ecdysone hormone in insects [5]. Gedunin, nimbin, and nimbolide isolated from Azadirachta indica and K. grandifoliola have been reported to have in vitro antimalarial activity on P. falciparum. According to Roy and Saraf (2006), the C-seco limonoids with an enone system in ring "A" are potent cytotoxic and antimalarial agents. Moreover, the C-seco limonoids are two to three times more active than other limonoids and they are also highly active against herbivorous insects [3]. e well-known insecticidal limonoids (azadirachtin, salannin, and nimbin) isolated from neem have been used as an active ingredient in a number of commercial insecticide formulations and marketed in many countries [6][7][8]. Over the years, the well-known limonoids and neem extracts were documented as successful examples of botanical insecticides commercialized. Based on the record of known safety, mode of action, and interaction of the limonoid active ingredients, the chemical class is expected to repurpose or use widely for controlling the phytopathogens in organic agriculture [9][10][11][12][13]. However, to our best knowledge, there are very few studies on the activity of Meliaceous limonoids against phytopathogenic fungi. Several antifungal limonoids against fungal plant pathogens have been studied and reported to occur in the fruits of Khaya senegalensis, K. ivorensis, and Aphanamixis polystachya. Zhang et al. (2013) identified prieurianin-type limonoids and aphanamolide-type limonoids from the fruits of A. polystachya and conducted some preliminary experiments to evaluate for their fungicidal, herbicidal, and insecticidal activities [14]. Methyl angolensate and 1, 3, 7-trideacetylkhivorin isolated from the fruits of K. ivorensis displayed a moderate inhibition against the mycelial growth of Botrytis cinerea, at 1000 and 1500 µg/mL [10]. From the fruits of K. senegalensis, Abdelgaleil et al. (2004) also successfully isolated bioactive limonoids such as seneganolide A, 2-acetoxyseneganolide A, and methyl 6-hydroxyangolensate with antifungal effects on B. cinerea [9]. In our ongoing research studies on bioactive limonoids from Meliaceous plants growing in Vietnam, we successfully isolated and identified nine limonoids from Melia dubia (1)(2), Aphanamixis polystachya (3)(4)(5), and Swietenia macrophylla (6)(7)(8)(9). e antifungal potential of the isolated limonoids against various phytopathogenic fungi including F. oxysporum, M. oryzae, S. rolfsii, R. solani, Alternaria spp., B. cinerea, and oomycetes Phytophthora species was evaluated in vitro.

Plant Materials.
e fruits of three species (Melia dubia, Aphanamixis polystachya, and Swietenia macrophylla) were collected from July to August 2017 from Pu Huong Nature Reserve, Nghe An Province; Vu Quang Nature Reserve, Ha Tinh Province; and Cat Tien National Park, Dong Nai Province, Vietnam, respectively. e plant materials were identified by Dr. Quoc Binh Nguyen, Vietnam National Museum of Nature, Vietnam Academy of Science and Technology, Hanoi, Vietnam. e voucher samples (no. MDF-072017, APF-082017, and SMF-082017) were deposited in the same museum.

Microbial Strains and Culture Conditions.
e in vitro antifungal activity of the botanical extracts and purified limonoids was tested based on poisoned food technique against nine phytopathogenic fungi including Fusarium oxysporum, Magnaporthe oryzae, Sclerotium rolfsii, Rhizoctonia solani, Botrytis cinerea, Alternaria spp., Phytophthora capsici, Phytophthora palmivora, and Phytophthora spp. Out of oomycetes Phytophthora species, Phytophthora spp. was isolated from the infected roots of Panax vietnamensis Ha et Grushv., and P. palmivora and P. capsici were isolated from the infected leaves of durian (Durio zibethinus) and black pepper (Piper nigrum), respectively. Potato dextrose broth (PDB) was used to subculture, and the potato dextrose agar (PDA) medium was used to culture fungal strains for antifungal tests at 20-25°C for 2-7 days.

Antifungal Activity Bioassays.
e organic soluble extracts and limonoids were tested for their in vitro antifungal activity by using the poisoned food technique. e tested materials were dissolved in DMSO or MeOH and then amended with a sterilized PDA medium in Petri dishes (4 cm and 6 cm diameters) to reach to final concentrations. e solvent content was not higher than 2% in the medium, and the amended dishes were let cooling at room temperature. All of the limonoids were treated in a range concentration of 37.5-500 µg/mL. Each Petri dish was inoculated with a mycelial plug in the center and incubated at 20-25°C for 2-7 days. e Petri dishes treated with 2% DMSO were used as negative controls. e positive controls treated with Score 250EC (a commercial fungicide containing 250 g/L of difenoconazole, Syngenta Vietnam Co. Ltd.) were tested against M. oryzae, S. rolfsii, and oomycetes at a dose of 1000fold dilution (equivalent to 250 µg of active ingredient/mL). All experiments for each fungal species were performed at least with two replicates. e diameter of mycelial growth was measured and recorded when fungal colonies nearly reached the edge of the negative control dishes. e percentage inhibition of mycelial growth (%) for the tested samples was calculated by using the formula: where A is the diameter of the mycelial growth of fungus in the negative control dishes (mm), B is the diameter of mycelial growth of fungus in treated dishes (mm), and 4 is the diameter of PDA plug of fungal inoculum (mm).
e inhibition values were presented as means ± standard deviation and evaluated by one-way analysis of variance (ANOVA). e half-maximal inhibitory concentration (IC 50 , µg/mL) of limonoids against the mycelial growth of the test fungi was computed from a dose-response inhibition curve by probit analysis of WINPEPI software version 11.63.  us, compound 1 (MD1) was assigned the structure of dysobinin, when its spectrums were compared to the literature [15,16]. e oxygenated methine at δ C 71.5 showed HMBC correlations to C 26 -H and C 27 -H and to the oxygenated methylene at δ C 83.3. e oxygenated methine at δ C 86.4 showed HMBC correlations to C 21 -H and C 17 -H. It could thus be concluded that the side chain contains an ether bridge between C 20 and C 24 while the second alcohol function (besides the one at C 3 ) is at C 25 . Because C 24 -H shows NOEs both to C 26 -H and to C 27 -H, the stereochemistry of C 24 must be rel S. e NOE between C 16 -Hα and C 23 -H leads to the conclusion that the configuration at C 20 is rel R. Again, this is in agreement with a C 20 -oxygenated tirucallane.
Compound  8 . e NMR spectrum of compound 3 showed five tertiary methyl groups and four methyl protons. e 13 C-NMR spectrum of compound 3 showed several similarities with that of compound 1. is indicated the presence of another tirucallane triterpene with differences in the side chain, which was evidenced only a change in the structural part of the lactone ring substitutes for the furan ring. e structure of compound 3 determined by 1D-and 2D-NMR experiments agreed as tirucallane-type triterpenoid. e spectral data of compound 3 (AP1) were identical with literature values for chisocheton compound G [18].

Journal of Chemistry
Compound 7 was isolated as colorless crystals. Its molecular formula was established as C 27 H 34 O 9 by the ESI-MS spectrum with m/z 503.1 [M + H] + and NMR spectral data. e structure of compound 7 could be deduced by comparing its NMR spectral data with those of compound 6. e 1 H and 13 C NMR spectral data of 7 suggested the presence of two double bonds (furan ring) and 4 carbonyl groups (3 ketones and 1 ester). ese NMR spectral data of compound 7 were identical with those of khayanone.
us, we can conclude that 7 (SM2) is khayanone [21]. e NMR spectra of compound 8 are mostly similar to those of compounds 6 and 7 except for some differences in the chemical shifts of C 1 , C 19 , and C 3 , suggesting 8 to have the type of phragmalin structure. e comparison of NMR data of compound 8 with the literature data [22] confirmed 8 (SM3) to be khayanolide B.
Compound 9 was purified as white powder. Its molecular formula was determined as C 29  structure of 9 revealed the presence of five methyl groups at δ H 0.92; 1.16; 1.47; 1.06; 2.20; and 3.77 by the 1 H NMR spectrum. Its 13 C NMR spectrum indicated the presence of 29 carbons, including 6 methyls, 5 methylenes, 8 methine groups, and 10 tertiary carbons. e β-furyl moiety and a methyl ester were also detected from its 13 C-NMR and DEPT spectra. Based on these data and the comparison with literature data [22], compound 9 (SM4) is indicated to be 6acetoxy-methyl angolensate.

In Vitro Antifungal Efficacy of the Isolated Limonoids.
In a preliminary study, we found that the methanol extracts of M. dubia, A. polystachya, and S. macrophylla suppress the mycelial growth of various phytopathogenic fungi at 1000 and 2000 µg/mL (Table S1). e pure limonoids were tested for their in vitro antifungal activity against nine phytopathogenic agents including F. oxysporum, M. oryzae, S. rolfsii, R. solani, Alternaria spp., and B. cinerea, and three oomycetes Phytophthora species. e development of mycelial growth of F. oxysporum and M. oryzae was affected by almost all the test limonoids. However, F. oxysporum was less sensitive to compounds 1 and 5 on the basis of the evidence of the mycelial growth inhibition at 250 and 500 µg/ mL (Table 1). e mycelial growth of this fungus was slightly suppressed by compounds 2, 3, 4, 6, and 8 (Table 1 and Figure 2). Compound 3 gave the highest inhibition (IC 50 � 480.5 µg/mL) for F. oxysporum (Table 2). e mycelial growth of M. oryzae, the causal agent of rice blast, was solidity suppressed when treated with 2, 3, 8, and 9 (Tables 1  and 2). At a concentration of 500 µg/mL, compounds 2, 8, and 9 also significantly reduced the mycelial growth of M. oryzae with inhibitions of 68.9%, 97.1%, and 66.0%, respectively, while compounds 1, 5, and 7 caused weak inhibitions (data not shown). e isolated limonoids 2, 3, 6, and 8 significantly suppressed the oomycetes Phytophthora spp., P. capsici, and P. palmivora at concentrations ranging from 62.5 to 500 µg/mL (Figure 3 and S2-4). Compounds 3 and 8 were the most potent limonoids against the tested oomycetes.
e IC 50 values of these four limonoids are presented in Table 2. At 250 and 500 µg/mL, compound 8 inhibited by 69.3% and 79.7% of the mycelial growth of Phytophthora spp., respectively (data not shown). Compound 3 displayed a dose-dependent activity against the test oomycetes Phytophthora spp. and P. capsici (Figure 2). is compound was also most active against Phytophthora spp and P. capsici; it caused 75.71% and 70.66% inhibition for the mycelial growth of the test oomycetes at 250 and 500 µg/mL, respectively ( Figure S2 and 3). Similar to the antifungal activity of 3, compound 8 also had a dose-dependent activity against Phytophthora spp. and P. capsici. However, it seems that the fungal efficacy of 8 (IC 50 � 97.1 µg/mL) was better than that of 3 (IC 50 � 178.5 µg/mL) when tested against Phytophthora spp. In contrast, the plant pathogens F. oxysporum, M. oryzae, and P. palmivora were strongly inhibited in the treatment with 3 compared with those with 8 (Figure 2, S2-4, and Table 2).
Besides, S. rolfsii was strongly inhibited by limonoids 2, 3, 6, and 8 in vitro (Table 1 and Figure 2). All of the four compounds displayed a dose-dependent antifungal activity against S. rolfsii. Compounds 2 and 6 were the best inhibitor against the mycelial growth of S. rolfsii with IC 50 values of 94.0 and 79.4 µg/mL, respectively. Compounds 3 and 8 also strongly inhibited this fungus with IC 50 values of 128.0 and 124.5 µg/mL, respectively ( Table 2).
Of the limonoids isolated from S. macrophylla (6-9), compounds 6-8 belong to mexicanolide-type limonoids. Compound 6 moderately inhibited the mycelial growth of R. solani (57.9%) while 8 did not when tested at a concentration of 250 µg/mL (data not shown). Compounds 6 (seneganolide) and 8 (khayanolide B) affected the mycelial growth of various oomycetes and fungi (Table 2 and Figure 2). Compounds 7 and 9 were isolated in a limited amount and were tested only with M. oryzae. Of those, limonoid 9 belonging to andirobin-type limonoid was highly active against M. oryzae.
e mycelial growth of B. cinerea, R. solani, and Alternaria spp. was also weakly inhibited by compounds 2, 3, 6, and 8 with an inhibition range of 12.8-34.8% at concentrations of 250 and 500 µg/mL (data not shown). All positive controls against the mycelial growth of M. oryzae, S. rolfsii, and oomycetes exhibited by 100% suppression when treated with difenoconazole at 250 µg/mL (data not shown).

Discussion
Limonoids are known as the main secondary metabolites produced by the plants from Melia and Citrus genera. e insecticidal limonoids have been applied to pest management in agriculture for a long time. However, the reports of the antifungal activity of limonoids from Meliaceae family have been rare until now. e notable antifungal activity of the three methanol extracts of M. dubia, A. polystachya, and S. macrophylla has prompted us to search the antifungal ingredients in the samples and evaluate their in vitro antifungal efficacy against phytopathogenic fungi. In our study, nine limonoids were tested for their antifungal activity against nine phytopathogenic fungi. Five potent antifungal limonoids 2, 3, 6, 8, and 9 significantly inhibited the test fungi in a broad spectrum. S. rolfsii was also found to be the best sensitive to the isolated limonoids 2, 3, 6, and 8; for this fungus, all of the compounds displayed a strong antifungal activity in a dose-dependent manner and IC 50 values in a range of 79.4-128.0 µg/mL ( Figure 2 and Table 2). F. oxysporum seemed to be less sensitive to all test fungi, except for compound 3 when tested at a concentration of 500 µg/mL. Remarkably, compounds 3 and 8 were the most active and showed a broad-spectrum antifungal activity against various fungal plant pathogens such as F. oxysporum, M. oryzae, and S. rolfsii, and the three oomycete strains of Phytophthora species. Compounds 1-5 belong to the class of ring D-opened limonoid, and the class includes some antifungal limonoids such as 3-deacetylkhivorin, 1, 3, 7-trideacetylkhivorin, 7-deacetylgedunin, and 7-deacetoxy-7-oxogedunin isolated from Khaya ivorensis and reported to be weakly and moderately active against the plant fungus Botrytis cinerea at the concentrations higher than 1000 µg/ mL [10].
A. polystachya grows abundantly in India, China, and Southeast Asia and has been used as medicinal materials in traditional medicine. e structural characterization and bioactivities of various limonoids from the fruits of A. polystachya were investigated in previous studies [3,23,24]. Especially, the reports of the antifungal activity of limonoids from this plant have been rare until now. Srivastava et al. (2003) reported the isolation of an andirobin-type limonoid named amoorinin-3-O-α-L-rhamnopyranosyl-(1-6)-ß-Dglucopyranoside from A. polystachya with antifungal activity against Aspergillus niger and Candida albicans [25]. In a previous study by Zhang et   In contrast, we reported here that compounds 3, 4, and 5 are isolated from A. polystachya and have a similar carbon skeleton except for the substitute attached to C-17 (4hydroxybut-2-enolide for 3, butanolide for 4, and furan ring for 5). Chisocheton compound G (3) showed the best mycelial growth inhibition against Phytophthora species, while 4 and 5 were almost inactive against the oomycete. is may be due to the structure of 3 contains 4-hydroxybut-2-enolide  moiety at C-17, which is similar to the head moiety of annonaceous acetogenins with a potential of antioomycete activity and cytotoxicity [26]. Swietenia species biosynthesize more than 160 limonoids including 77 mexicanolide-type limonoids (most from S. mahagoni and S. macrophylla).
e Meliaceous plant S. macrophylla grows widely in Central and South American countries, India, Malaysia, and China [1,4]. It is rare to see in Vietnam, and the phytochemical investigation, as well as antifungal properties of the local species, has not been reported much. From the dried fruits of S. macrophylla growing in Vietnam, four limonoids 6-9 were isolated by various chromatographic methods. Out of them, mexicanolide-type limonoids seneganolide (6) and khayanolide B (8) showed the best antioomycete activity against Phytophthora species. Especially, khayanolide B (8) was the most active against M. oryzae, Phytophthora spp., and P. capsici. In the same group of mexicanolide carbon skeleton, three limonoids seneganolide A, 2-acetoxyseneganolide A, and methyl 6-hydroxyangolensate were reported to isolate from the fruits of Khaya senegalensis and tested against phytopathogenic fungus Botrytis cinerea at relatively high concentrations of 1000 and 1500 µg/mL. Limonoid 2acetoxyseneganolide A suppressed the mycelial growth of B. cinerea at 1000 µg/mL (61.50%) and 1500 µg/mL (68.33%), while seneganolide A and methyl 6-hydroxyangolensate showed a weaker inhibition [9]. Khayanolide B (8) was also reported as an antifeedant substance against Spodoptera littoralis with an EC 50 of 2.19 mg/kg [2]. Limonoid swietenolide isolated from S. macrophylla was documented to have antifeedant activity with antifeedant index of 94.1 against fall armyworm (Spodoptera frugiperda). 6-O-acetylswietenolide, 3, 6-O, O-diacetylswietenolide, and swietemahonin F exhibited antifeedant indices of 72.2, 72.0, and 70.2, respectively [1]. According to Sun et al. (2018), swietenine from this plant also showed the greatest potency with a 50% antifeedant index concentration of 2.49 against S. frugiperda [4].
As for the source rich in limonoids in Meliaceae species, A. indica and M. dubia have been described as potential plant systems that contain a wide range of bioactive limonoids that are both chemically and structurally complex [27]. Salannin, a well-known insecticidal limonoid, was found to be produced by A. indica and M. dubia. e bark of M. dubia was also reported to contain cytotoxic euphane-type triterpenes against P388 cancer cells [7]. However, there are no reports on antifungal activity of M. dubia against phytopathogenic fungi up to now. In a preliminary study by Mahmoud et al. (2011), the extracts derived from the leaves and seeds of A. indica were assessed for antifungal activity against six human fungal pathogens Aspergillus flavus, A. fumigatus, A. Niger, A. terreus, C. albicans, and M. gypseum [28]. Nimonol with a molecular formula of C 28 H 36 O 5 was separated and identified as the main compound of ethyl acetate extract of A. indica, but it displayed no inhibitory effect on all the six fungal pathogens tested [28]. In contrast, Alvarez-Caballero and Coy-Barrera (2019) described that azadirone-type limonoids such as nimonol, 14, 15-epoxynimonol, isomeldenin, zafaral, and O-acetyl-7-deacetylnimocinol isolated from A. indica possess a good inhibition against conidia germination of F. oxysporum. Nimonol was the best inhibitor; of which inhibition against F. oxysporum conidia germination was observed at IC 50 of 1.48 µM. Alvarez-Caballero and Coy-Barrera (2019) also demonstrated that the presence of a 14, 15-epoxy group and the saturation at 1, 2-olefilic positions in the structure of azadirone-type limonoids led to a diminished effect on fungal conidia germination [11]. In our study, 1, 3, 4, and 5 were isolated and identified as azadirone-type limonoids. Among them, compound 3 showed a broad-spectrum activity with potent suppression against almost all of the test fungi in the concentration ranging from 37.5 to 500 µg/mL ( Table 2 and Figure 2), while compounds 1, 4 and 5 showed a little effect on the growth of F. oxysporum and M. grisea. is suggested an implication of structure-antifungal activity relationship of the studied azadirone-type limonoids. e 2hydroxybutanolide groups at C-17 in the structure of 3 may make an enhancing effect on inhibition against fungi. Concerned to the antifungal activity of azadirone-type limonoids, 6α-acetoxyazadirone and 1, 2-dihydro-6α-acetoxyazadirone were also briefly reported to possess strong antifungal activity against pathogenic fungi Curvularia verruciformis, Dreschleva oryzae, and A. solani, but no information of inhibition effectiveness, biological testing methods, and test concentration was provided in the article [8,29]. According to Govindachari et al. (1998), the neem oil derived from the seeds of A. indica showed antifungal activity against phytopathogenic fungi and contains an abundance of limonoids such as azadiradione, nimbin, 6deacetylnimbin, salannin, and epoxyazadiradione [12]. However, these compounds in pure form have not much affected the mycelial growth of D. oryzae, F. oxysporum f.sp. vasinfectum, and Alternaria tenuis at a high concentration of 1000 µg/mL. Only 6-deacetylnimbin and nimbin inhibited D. oryzae, the causal agent of rice brown leaf spot disease, by 63.3 and 64.8%, respectively. Besides, either additive or synergistic influence of the mixture containing those terpenoids was observed with an inhibition of 70% for D. oryzae at 1000 µg/mL [12].
As for the antifungal effects on soilborne plant pathogenic fungi, Sharma et al. (2003) reported that azadirachtins A, B, and H possessing antifungal potential against R. solani and S. rolfsii were efficiently isolated from the seed kernels of A. indica. Azadirachtin A inhibited the mycelial growth of R. solani and S. rolfsii at ED 50 values of 104.8 µg/mL (purity of 90% for azadirachtin A) and 93.6 µg/mL, respectively. Azadirachtins B and H exhibited a better inhibition with ED 50 values varying from 43.9 to 85.9 µg/mL for the two fungi [30]. erefore, in addition to azadirachtins A, B, and H belonging to the ring C-seco limonoid group, the isolated compounds 2, 3, 6, and 8 in our study are different structure type limonoids with potent inhibition against S. rolfsii were consequently reported.
Our study has described the antifungal property of the limonoids isolated from A. polystachya, M. dubia, and S. macrophylla against various phytopathogenic fungi for the first time. To discover more potent antifungal limonoids, experiments in the mode of action and the relationship between structures and antifungal activity of limonoids need to conduct. In further studies, the in vivo antifungal efficacy and phytotoxicity of the bioactive limonoids, which could be formulated evenly into a ready-to-use formulation, should be evaluated to determine their potential disease control efficacy on various crops.

Conclusions
Considering the application of limonoids in crop protection, in our work, the chemical structural characterization and antifungal activity evaluation of nine limonoids isolated from M. dubia (1-2), A. polystachya (3)(4)(5), and S. macrophylla (6-9) were described and pointed our promising active compounds against various phytopathogenic fungi. Limonoids 2, 3, 6, 8, and 9 were found to be promising candidates with a broad antifungal spectrum. Compounds 2, 8, and 9 displayed moderate activity against M. oryzae, while S. rolfsii and Phytophthora species were the most susceptible species to the test limonoids. It is noteworthy that chisocheton compound G (3) isolated from A. polystachya and khayanolide B (8) isolated from S. macrophylla were the most potent antifungal limonoids against M. oryzae and Phytophthora species. Our findings may suggest and encourage more work on the discovery of antifungal limonoids and lead compounds from the group of limonoids.

Data Availability
e data used to support the findings of this study are included in the supplementary materials and available from the corresponding authors upon request.

Conflicts of Interest
e authors declare no conflicts of interest.

Authors' Contributions
ang Tran Dinh, Hoang Dinh Vu, Dang Ngoc Quang, and Quang Le Dang were responsible for conceptualization, methodology, and supervision.
anh Nguyen Tan, Hieu Tran Trung, Tuan Nguyen Ngoc, Hien Vu i, Dang Ngoc Quang, and ang Tran Dinh were responsible for extraction, purification, and structure identification for isolated compounds. anh Huong Nguyen, Hoai u i Do, and Quang Le Dang were responsible for antifungal bioassay and biological data analysis. anh Nguyen Tan, Hoai u i Do, Quang Le Dang, and ang Tran Dinh were responsible for writing -original draft preparation, and editing. All authors read and approved the submitted manuscript. Figure S1a: isolation scheme of isolated compounds 1-2 from the fruits of Melia dubia. Figure S1b: isolation scheme of isolated compounds 3-5 from the fruits of Aphanamixis polystachya. Figure S1c: isolation scheme of isolated compounds 6-9 from the fruits of Swietenia macrophylla. Figure  S2: in vitro antifungal activity of the most active compounds 3 and 8 against the mycelial growth of Phytophthora spp. Figure S3: in vitro antifungal activity of the most active compounds 3 and 8 against the mycelial growth of Phytophthora capsici. Figure S4: in vitro antifungal activity of the most active compounds 3, 6, and 8 against the mycelial growth of Phytophthora palmivora. Figure S5: in vitro antifungal activity of compound 2 against the mycelial growth of Magnaporthe oryzae. Figure S6: in vitro antifungal activity of the most active compounds 2, 3, 6, and 8 against the mycelial growth of Sclerotium rolfsii.