Synthesis of Bioactive Compounds from 3-Carene (II): Synthesis, Antifungal Activity and 3D-QSAR Study of (Z)- and (E)-3-Caren-5-One Oxime Sulfonates.
ABSTRACT: A series of novel (Z)- and (E)-3-caren-5-one oxime sulfonates were designed and synthesized in search of potent antifungal agents. The structures of the intermediates and target compounds were confirmed by UV-Vis, FTIR, NMR, and ESI-MS. The in vitro antifungal activity of the target compounds was preliminarily evaluated against Cercospora arachidicola, Physalospora piricola, Alternaria solani, Rhizoeotnia solani, Bipolaris maydis and Colleterichum orbicalare at 50 µg/mL. The bioassay results indicated that the target compounds exhibited the best antifungal activity against P. piricola, in which compounds 4b, 4f, 4m, 4e, 4j, 4l, 4y, 4d, and 4p had excellent inhibition rates of 100%, 100%, 100%, 92.9%, 92.9%, 92.9%, 92.9%, 85.7%, and 85.7%, respectively, showing much better antifungal activity than that of the commercial fungicide chlorothanil. Both the compounds 4y and 4x displayed outstanding antifungal activity of 100% against B. myadis, and the former also displayed outstanding antifungal activity of 100% against R. solani. In order to design more effective antifungal compounds against P. piricola, the analysis of three-dimensional quantitative structure-activity relationship (3D-QSAR) was carried out using the CoMFA method, and a reasonable and effective 3D-QSAR model (r² = 0.990, q² = 0.569) has been established.
Project description: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-NO? 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.
Project description:A series of novel 3-caren-5-one oxime esters were designed and synthesized by multi-step reactions in an attempt to develop potent antifungal agents. Two E-Z stereoisomers of the intermediate 3-caren-5-one oxime were separated by column chromatography for the first time. The structures of all the intermediates and target compounds were confirmed by UV-Vis, FTIR, NMR, ESI-MS, and elemental analysis. The 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, Gibberella zeae,Rhizoeotnia solani, Bipolaris maydis, and Colleterichum orbicalare at 50 µg/mL. The target compounds exhibited best antifungal activity against P. piricola, in which compounds (Z)-4r (R = ?-pyridyl), (Z)-4q (R = ?-thienyl), (E)-4f' (R = p-F Ph), (Z)-4i (R = m-Me Ph), (Z)-4j (R = p-Me Ph), and (Z)-4p (R = ?-furyl) had inhibition rates of 97.1%, 87.4%, 87.4%, 85.0%, 81.9%, and 77.7%, respectively, showing better antifungal activity than that of the commercial fungicide chlorothanil. Also, compound (Z)-4r (R = ?-pyridyl) displayed remarkable antifungal activity against all the tested fungi, with inhibition rates of 76.7%, 82.7%, 97.1%, 66.3%, 74.7%, 93.9%, 76.7% and 93.3%, respectively, showing better or comparable antifungal activity than that of the commercial fungicide chlorothanil. Besides, the E-Z isomers of the target oxime esters were found to show obvious differences in antifungal activity. These results provide an encouraging framework that could lead to the development of potent novel antifungal agents.
Project description:A series of (R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a diacylhydrazine moiety were designed and synthesized. Their structures were confirmed by melting points, 1H NMR, 13C NMR, and elemental analysis (EA). Their antifungal and insecticidal activities were evaluated. The antifungal activity result indicated that most title compounds against Cercospora arachidicola, Alternaria solani, Phytophthora capsici, and Physalospora piricola exhibited apparent antifungal activities at 50 mg/L, and better than chlorothalonil or carbendazim. The EC50 values of (R)-N'-benzoyl-2-(4-chlorophenyl)-4,5-dihydrothiazole-4-carbohydrazide (I-5) against six tested phytopathogenic fungi were comparable to those of chlorothalonil. The CoMSIA model showed that a proper hydrophilic group in the R1 position, as well as a proper hydrophilic and electron-donating group in the R2 position, could improve the antifungal activity against Physalospora piricola, which contributed to the further optimization of the structures. Meanwhile, most title compounds displayed good insecticidal activities, especially compound (R)-N'-(4-nitrobenzoyl)-2-(4-nitrophenyl)-4,5-dihydrothiazole-4-carbohydrazide (III-3). The insecticidal mechanism results indicated that compound III-3 can serve as effective insect Ca2+ level modulators by disrupting the cellular calcium homeostasis in Mythimna separata.
Project description:Twenty-seven (<i>Z</i>)- and (<i>E</i>)-verbenone derivatives bearing an oxime ester moiety were designed and synthesized in search of novel bioactive molecules. Their structures were confirmed by UV-Vis, FTIR, NMR, ESI-MS, and elemental analysis. The antifungal and herbicidal activities of the target compounds were preliminarily evaluated. As a result, compound (<i>E</i>)-<b>4n</b> (R = <i>?</i>-pyridyl) exhibited excellent antifungal activity with growth inhibition percentages of 92.2%, 80.0% and 76.3% against <i>Alternaria solani</i>, <i>Physalospora piricola</i>, and <i>Cercospora arachidicola</i> at 50 µg/mL, showing comparable or better antifungal activity than the commercial fungicide chlorothalonil with growth inhibition of 96.1%, 75.0% and 73.3%, respectively, and 1.7-5.5-fold more growth inhibition than its stereoisomer (<i>Z</i>)-<b>4n</b> (R = <i>?</i>-pyridyl) with inhibition rates of 22.6%, 28.6% and 43.7%, respectively. In addition, seven compounds displayed significant growth inhibition activity of over 90% against the root of rape (<i>Brassica campestris</i>) at 100 µg/mL, exhibiting much better herbicidal activity than the commercial herbicide flumioxazin with a 63.0% growth inhibition. Among these seven compounds, compound (<i>E</i>)-<b>4n</b> (R = <i>?</i>-pyridyl) inhibited growth by 92.1%, which was 1.7-fold more than its stereoisomer (<i>Z</i>)-<b>4n</b> (R = <i>?</i>-pyridyl) which inhibited growth by 54.0%.
Project description:A series of linear furanocoumarins with different substituents have been designed and synthesized. Their structures were confirmed by ¹H-NMR spectroscopy, high resolution mass spectra (EI-MS), IR, and X-ray single-crystal diffraction. All of the target compounds were evaluated in vitro for their antifungal activity against Rhizoctorzia solani, Botrytis cinerea, Alternaria solani, Gibberella zeae, Cucumber anthrax, and Alternaria leaf spot at 100 ?g/mL, and some of the designed compounds exhibited potential antifungal activities. Compound 3a (67.9%) exhibited higher activity than the control Osthole (66.1%) against Botrytis cinerea. Furthermore, compound 4b (62.4%) represented equivalent antifungal activity as Osthole (69.5%) against Rhizoctonia solani. The structure-activity relationship (SAR) study demonstrates that linear furanocoumarin moiety has an important effect on the antifungal activity, promoting the idea of the coumarin ring as a framework that might be exploited in the future.
Project description:A new microwave method (MM) has been developed for the synthesis of a series of 16 substituted ferrocenyl chalcones using acetylferrocene (1) with different aldehydes (2a-2p) and comparing it with conventional method (CM). The synthesized compounds were characterized by various spectroscopic techniques viz IR, HR-MS, 1H NMR, and 13C NMR. The time required for completion of reaction in MM varied from 1 to 5 min as compared to CM which required 10-40 h. All the synthesized compounds were screened for antifungal activity against Sclerotium rolfsii and Alternaria solani. In vitro fungicidal activity revealed that compound 3o (ED50 = 23.24 mg L-1) was found to be most active against S. rolfsii. But in case of A. solani, compound 3c (ED50 = 29.9 mg L-1) showed highest activity. The nematicidal activity revealed that the compound 3b was more potent with LC50 values of 10.67, 7.30, and 4.55 ppm at 24, 48, and 72 h, respectively. 2D-Quantitative Structural Activity Relationship (2D-QSAR) analysis of these ferrocenyl chalcones was carried out by developing three different models namely Partial Least Squares (PLS, Model 1), Multiple Linear Regression (MLR, Model 2) and Principal Component Regression (PCR, Model 3). Statistical significance and predictive ability of these models were assessed by internal and external validation and also verified by leave one-out cross-validation. QSAR study revealed that MLR for S. rolfsii (r 2 = 0.999, q 2 = 0.996), PLS for A. solani (r 2 = 0.934, q 2 = 0.749) and PCR for M. incognita (r 2 = 0.878, q 2 = 0.772) were the best model. The physico-chemical parameters were calculated using VLife MDS 4.6 software. QSAR study could be employed for structure optimization to achieve better activity.
Project description:Streptomyces strain KX852460 having antifungal activity against Rhizoctonia solani AG-3 KX852461 that is the causal agent of target spot disease in tobacco leaf. The aim of the study was to determine the antifungal activity of Streptomyces strain KX852460 extract against R. solani AG-3 and to identify bioactive antifungal compounds produced by strain KX852460. Crude substance was produced by submerged fermentation process from Streptomyces strain KX852460. Various solvent was used to extract the culture filtrate. Among all, ethyl acetate extracted supernatant showed great potency against R. solani AG-3 KX852461. The active fractions were purified by silica gel column chromatography having 52 mm zone of inhibition against R. solani AG-3 KX852461. The purified fractions were identified by gas chromatography-mass spectrometry technique. Twenty-seven compounds were identified and most of the compounds were the derivatives of aromatic compounds. Eicosane (C20H42) and dibutyl phthalate (C16H22O4) were found antifungal compounds in this study. While morphinan, 7,8-didehydro-4,5-epoxy-17-methyl-3,6-bis[(trimethylsilyl)oxy]-, (5.Alpha. 6.Alpha)-(C23H35NO3Si2), cyclononasiloxane, octadecamethyl-(C18H54O9Si9) and benzoic acid, 2,5-bis(trimethylsiloxy) (C16H30O4Si3) were the major compounds with highest peak number. These results suggested that Streptomyces strain KX852460 had good general antifungal activity and might have potential biocontrol antagonist against R. solani AG-3 KX852461 to cure the target spot in tobacco leaf.
Project description:Cinnamaldehyde amino acid Schiff base (CAAS) is a new class of safe, bioactive compounds which could be developed as potential antifungal agents for fungal infections. To design new cinnamaldehyde amino acid Schiff base compounds with high bioactivity, the quantitative structure-activity relationships (QSARs) for CAAS compounds against Aspergillus niger (A. niger) and Penicillium citrinum (P. citrinum) were analysed. The QSAR models (R2?=?0.9346 for A. niger, R2?=?0.9590 for P. citrinum,) were constructed and validated. The models indicated that the molecular polarity and the Max atomic orbital electronic population had a significant effect on antifungal activity. Based on the best QSAR models, two new compounds were designed and synthesized. Antifungal activity tests proved that both of them have great bioactivity against the selected fungi.
Project description:As part of our continuing research on canthin-6-one antimicrobial agents, a new series of ester derivatives of 10-hydroxycanthin-6-one were synthesized using a simple and effective synthetic route. The structure of each compound was characterized by NMR, ESI-MS, FT-IR, UV, and elemental analysis. The antimicrobial activity of these compounds against three phytopathogenic fungi (Alternaria solani, Fusarium graminearum, and Fusarium solani) and four bacteria (Bacillus cereus, Bacillus subtilis, Ralstonia solanacearum, and Pseudomonas syringae) were evaluated using the mycelium linear growth rate method and micro-broth dilution method, respectively. The structure-activity relationship is discussed. Of the tested compounds, 4 and 7s displayed significant antifungal activity against F. graminearum, with inhibition rates of 100% at a concentration of 50 ?g/mL. Compounds 5, 7s, and 7t showed the best inhibitory activity against all the tested bacteria, with minimum inhibitory concentrations (MICs) between 3.91 and 31.25 ?g/mL. Thus, 7s emerged as a promising lead compound for the development of novel canthine-6-one antimicrobial agents.
Project description:Two series of novel cuminaldehyde derivatives containing pyrazoline and isoxazoline moieties have been designed and synthesized. All of the compounds were characterized <i>via</i> <sup>1</sup>H-NMR,<sup>13</sup>C-NMR, and HRMS. The antifungal activities were evaluated against six plant-pathogenic fungi. 3-(2-Fluorophenyl)-5-(4-isopropylphenyl) isoxazoline (<b>2d</b>) and 1-acetyl-3-(2-fluorophenyl)-5-(4-isopropylphenyl)-2-pyrazoline (<b>3d</b>) displayed higher antifungal activities than commercial fungicides against <i>Sclerotinia sclerotiorum</i>, <i>Physalospora piricola</i> and <i>Pyricularia oryzae</i>. The title compounds (<b>2d</b> and <b>3d</b>) with strong antifungal activities are worth being further evaluated <i>in vivo</i> and in the field.