A series of novel myrtenal derivatives bearing 1,2,4-triazole moiety were designed and synthesized by multi-step reactions in an attempt to develop potent antifungal agents. Their structures were confirmed by using UV-vis, FTIR, NMR, and ESI-MS analysis. Antifungal activity of the target compounds was preliminarily evaluated by the in vitro method against Fusarium oxysporum f. sp. cucumerinum, Physalospora piricola, Alternaria solani, Cercospora arachidicola, and Gibberella zeae at 50 µg/mL. Compounds 6c (R = i-Pr), 6l (R = o-NO₂ Bn), and 6a (R = Et) exhibited excellent antifungal activity against P. piricola with inhibition rates of 98.2%, 96.4%, and 90.7%, respectively, showing better or comparable antifungal activity than that of the commercial fungicide azoxystrobin with a 96.0% inhibition rate, which served as a positive control.

A series of novel nopol derivatives bearing the 1,3,4-thiadiazole-thiourea moiety were designed and synthesized by multi-step reactions in search of potent natural product-based antifungal agents. Their structures were confirmed by FT-IR, NMR, ESI-MS, and elemental analysis. Antifungal activity of the target compounds was preliminarily evaluated by in vitro methods against Fusarium oxysporum f. sp. cucumerinum, Cercospora arachidicola, Physalospora piricola, Alternaria solani, Gibberella zeae, Rhizoeotnia solani, Bipolaris maydis, and Colleterichum orbicalare at 50 µg/mL. All the target compounds exhibited better antifungal activity against P. piricola, C. arachidicola, and A. solani. Compound 6j (R = m, p-Cl Ph) showed the best broad-spectrum antifungal activity against all the tested fungi. Compounds 6c (R = m-Me Ph), 6q (R = i-Pr), and 6i (R = p-Cl Ph) had inhibition rates of 86.1%, 86.1%, and 80.2%, respectively, against P. piricola, much better than that of the positive control chlorothalonil. Moreover, compounds 6h (R = m-Cl Ph) and 6n (R = o-CF₃ Ph) held inhibition rates of 80.6% and 79.0% against C. arachidicola and G. zeae, respectively, much better than that of the commercial fungicide chlorothalonil. In order to design more effective antifungal compounds against A. solani, analysis of the three-dimensional quantitative structure–activity relationship (3D-QSAR) was carried out using the CoMFA method, and a reasonable and effective 3D-QSAR model (r² = 0.992, q² = 0.753) has been established. Furthermore, some intriguing structure–activity relationships were found and are discussed by theoretical calculation.

Succinate dehydrogenase (SDH) present in the inner mitochondrial membrane is an important target enzyme for the design of SDH inhibitor-type fungicides. Using SDH as the target enzyme, 22 novel longifolene-derived diacylhydrazine compounds were designed and synthesized using the renewable natural product longifolene as the starting material. Their structures were confirmed by IR, ¹H NMR, ¹³C NMR, electrospray mass spectrometry, and elemental analysis. In vitro antifungal activity of the target compounds was preliminarily evaluated. As a result, some of them showed better or comparable antifungal activity than that of the commercial fungicide chlorothalonil, in which compound 5a had inhibitory rates of 97.5, 80.5, 72.1, and 67.1% against Physalospora piricola, Colletotrichum orbiculare, Alternaria solani, and Gibberella zeae, respectively, presenting excellent and broad-spectrum activity that deserved further study. Besides, a reasonable and effective three-dimensional structure–activity quantitative relationship model has been established. There was a significant positive correlation between the antifungal activity and the docking-based binding energy analyzed using Spearman’s rank correlation algorithm. Also, the simulative binding pattern of the target compounds with SDH was investigated by molecular docking study. Furthermore, the diacylhydrazine and phenol groups of the target compounds were proposed to be the potential pharmacophores by frontier molecular orbital analysis.

In order to develop novel chemotherapeutic agents with potent anticancer activities, a series of dehydroabietic acid (DHA) derivatives bearing an acylhydrazone moiety were designed and synthesized by the condensation between dehydroabietic acylhydrazide (3) and a variety of substituted arylaldehydes. The inhibitory activities of these compounds against CNE-2 (nasopharynx), HepG2 (liver), HeLa (epithelial cervical), and BEL-7402 (liver) human carcinoma cell lines were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in vitro. The screening results revealed that many of the compounds showed moderate to high levels of anticancer activities against the tested cancer cell lines and some displayed similar potent inhibitory activities to the commercial anticancer drug cisplatin, while they exhibited lower cytotoxicity against normal human liver cell (HL-7702). Particularly, compound 4w, N’-(3,5-difluorobenzylidene)-2-(dehydroabietyloxy)acetohydrazide, with an IC₅₀ (50% inhibitory concentration) value of 2.21 μM against HeLa cell, was about 17-fold more active than that of the parent compound, and showed remarkable cytotoxicity with an IC₅₀ value of 14.46 μM against BEL-7402 cell. These results provide an encouraging framework that could lead to the development of potent novel anticancer agents.

A series of novel menthol derivatives containing 1,2,4-triazole-thioether moiety were designed, synthesized, characterized structurally, and evaluated biologically to explore more potent natural product-based antifungal agents. The bioassay results revealed that at 50 μg/mL, some of the target compounds exhibited good inhibitory activity against the tested fungi, especially against Physalospora piricola. Compounds 5b (R = o-CH₃ Ph), 5i (R = o-Cl Ph), 5v (R = m,p-OCH₃ Ph) and 5x (R = α-furyl) had inhibition rates of 93.3%, 79.4%, and 79.4%, respectively, against P. piricola, much better than that of the positive control chlorothalonil. Compounds 5v (R = m,p-OCH₃ Ph) and 5g (R = o-Cl Ph) held inhibition rates of 82.4% and 86.5% against Cercospora arachidicola and Gibberella zeae, respectively, much better than that of the commercial fungicide chlorothalonil. Compound 5b (R = o-CH₃ Ph) displayed antifungal activity of 90.5% and 83.8%, respectively, against Colleterichum orbicalare and Fusarium oxysporum f. sp. cucumerinum. Compounds 5m (R = o-I Ph) had inhibition rates of 88.6%, 80.0%, and 88.0%, respectively, against F. oxysporum f. sp. cucumerinu, Bipolaris maydis and C. orbiculare. Furthermore, compound 5b (R = o-CH₃ Ph) showed the best and broad-spectrum antifungal activity against all the tested fungi. To design more effective antifungal compounds against P. piricola, 3D-QSAR analysis was performed using the CoMFA method, and a reasonable 3D-QSAR model (r² = 0.991, q² = 0.514) was established. The simulative binding pattern of the target compounds with cytochrome P450 14α-sterol demethylase (CYP51) was investigated by molecular docking.

In search of novel compounds with both survivin inhibitory activity and fluorescence properties, 18 novel longifolene-derived tetralin pyrimidine compounds were designed using survivin as the target and synthesized from the sustainable natural resource longifolene. Their structures were confirmed by IR, NMR, ESIMS, and elemental analysis. The in vitro antiproliferative activities of the target compounds were preliminarily evaluated by standard MTT assay against MGC-803 (human gastric cancer cell), T24 (human bladder cancer cell), HepG2 (human liver cancer cell), and A549 (human lung adenocarcinoma cell). As a result, some of the target compounds showed better antiproliferative activities than that of the positive control drug 5-FU, in which, compound 5m had the IC50 1.42 µM against MGC-803 and compound 5l had the IC50 1.79 µM against T24, exhibiting excellect activity. Additionally, the target compounds display moderate or even low cytotoxicity toward human normal liver cells L02. Subsequently, a reasonable and effective 3D-QSAR model was established to study the relationship between the structure of the target compounds and antiproliferative activities and was employed to construct two new compounds with potentially better activity. Meanwhile, molecular docking was performed to study the interaction mode between compound 5m and survivin protein. Furthermore, the target compounds with significant antiproliferative activity showed noticeable fluorescence properties.