Synthesis, Antifungal Activity, Cytotoxicity and QSAR Study of Camphor Derivatives

Abstract

Control of fungal phytopathogens affecting crops and woodlands is an important goal in environmental management and the maintenance of food security. This work describes the synthesis of 37 camphor derivatives, of which 27 were new compounds. Their antifungal effects on six fungi were evaluated in vitro. Compounds 3a, 4a and 5k showed strong antifungal activity against Trametes versicolor, with EC50 values of 0.43, 6.80 and 4.86 mg/L, respectively, which were better than that of tricyclazole (EC50 118.20 mg/L) and close to or better than that of carbendazim (EC50 1.20 mg/L). The most potent compound, 3a, exhibited broad-spectrum antifungal activity towards six fungi with EC50 values within the range of 0.43–40.18 mg/L. Scanning electron microscopy demonstrated that compounds 3a, 4a and 5k gave irregular growth and shriveling of the mycelia. In vitro cytotoxicity evaluation revealed that the tested camphor derivatives had mild or no cytotoxicity for LO2 and HEK293T cell lines. Quantitative structure−activity relationship (QSAR) analysis revealed that the number of F atoms, relative molecular weight, the atomic orbital electronic population and total charge on the positively charged surfaces of the molecules of camphor derivatives have effects on antifungal activity. The present study may provide a theoretical basis for a high-value use of camphor and could be helpful for the development of novel potential antifungals.

Antifungal Activity and Mechanism of Camphor Derivatives against Rhizoctonia solani: A Promising Alternative Antifungal Agent for Rice Sheath Blight

“…Compounds 4k and 4o were evaluated for cytotoxicity against cell lines of LO2 and HEK293 using an MTT assay. As shown in Figure , the results indicated that compounds 4k and 4o had no cytotoxicity against LO2 and HEK293 cell lines at the concentration of 10 μg/mL, and the cell survival rate was close to 100%, which was correlated with our previous findings on camphor derivatives exhibiting low toxicity (nontoxic) for LO2 and HEK293T cells …”

“…solani was obtained via inoculation of potato dextrose agar (PDA) plates at 28 °C for 3 days. All reagents were purchased from Shanghai Macklin Biochemical Co., Ltd. (Shanghai, China) and Aladdin Chemical Reagent Co., Ltd. Camphor derivatives were synthesized using the previous methods and confirmed through Fourier transform infrared spectroscopy, hydrogen nuclear magnetic resonance ( 1 H NMR), carbon nuclear magnetic resonance ( 13 C NMR), and high-resolution mass spectrometry …”

“…Therefore, structural modification of active natural plant products has emerged as a promising approach for developing new fungicides. − Camphor is an important terpene ketone isolated from Cinnamomum camphor wood or synthetically produced via isomerization–oxidation of turpentine . Camphor and its derivatives, known for their wide-ranging biological activities, have been explored in various fields. − In our previous research, two series of novel thiosemicarbazone-camphor derivatives were designed and synthesized (Scheme ), and most compounds exhibited moderate to potent inhibitory activity against plant pathogenic fungi, such as Trametes versicolor, Fusarium oxysporum, and Colletotrichum gloeosporioides . However, its inhibitory effects and mode of action on R.…”

Design, Synthesis, and Biological Evaluation of Novel Camphor-Based Hydrazide and Sulfonamide Derivatives as Laccase Inhibitors against Plant Pathogenic Fungi/Oomycetes

“…As an important renewable natural monoterpene, camphor can be isolated from Cinnamomum camphora, while the synthetic analogue can be produced from turpentine . Camphor has been extensively utilized as a fragrance and food a flavorant in household cleaners as well as a component of hygienic insecticides. − Moreover, camphor has been used for the synthesis of many derivatives, which exhibited diverse pharmaceutical activities (Figure b). , Among them, some camphor derivatives were found to exhibit promising antifungal activities against different plant pathogenic fungi. , In addition, camphanic acid was a downstream product of camphor, and its derivatives also displayed promising pharmaceutical activities. For instance, Gerard et al reported that the amide derivatives of camphanic acid showed considerable antidiabetic activity (Figure b) .…”

“…26−28 Moreover, camphor has been used for the synthesis of many derivatives, which exhibited diverse pharmaceutical activities (Figure 1b). 29,30 Among them, some camphor derivatives were found to exhibit promising antifungal activities against different plant pathogenic fungi. 31,32 In addition, camphanic acid was a downstream product of camphor, and its derivatives also displayed promising pharmaceutical activities.…”