柠檬醛基抗油茶炭疽病菌衍生物的定量构效关系研究

doi:10.3969/j.issn.1673-5854.2021.01.007

摘要/Abstract

摘要：

为探讨柠檬醛基衍生物的结构与其对油茶炭疽病菌的抗菌活性之间的关系，研究了柠檬醛基抗油茶炭疽病菌衍生物的定量构效关系。使用计算化学软件Gauss View05、Gaussian 09W、Ampac和Codessa分别完成了柠檬醛基衍生物分子结构的构建、优化、描述符计算与筛选，以及QSAR模型建立。结果表明：建立了一个含有4个描述符：氢原子之间的相互斥力、分子中带正电荷加权部分表面积比例、氢原子的数量、分子表面正电荷分布以及分子总表面积的最佳QSAR模型，相关系数(R²)为0.926 5。对最佳QSAR模型进行内部检验和外部检验，其中留一法内部检验的R_CV²=0.865 7，三重内部检验的R_training²=0.879 3、R_test²=0.882 4；外部检验的R_外²=0.946 7，表明该模型具有良好的稳定性和预测能力。解析建模描述符可知，柠檬醛基衍生物分子结构中与氢键供体相关的描述符对抗菌活性具有显著影响。本研究可为新型柠檬醛抗油茶炭疽病菌衍生物的设计与合成提供理论指导。

关键词: 柠檬醛, 衍生物, 定量构效关系, 启发式回归

Abstract:

In order to investigate the relationship between the structure of citral derivatives and their antifungal activities against Colletotrichum gloeosporioides, the quantitative structure-activity relationship study of citral-based derivatives against C. gloeosporioides was carried out. The computational chemistry softwares GaussView 05, Gaussian 09W, Ampac and Codessa were used to finish the molecular structure optimization, descriptor calculation and screening, and QSAR model construction. The results showed that the best QSAR model with four descriptors, including Min e-e repulsion for a H atom; ESP-FPSA-3 Fractional PPSA(PPSA-3/TMSA); number of H atoms; WPSA-3 Weighted PPSA(PPSA-3^*TMSA/1000), were established, and its correlation coefficient (R²) was 0.926 5. Internal validation and external validation of the best QSAR model were carried out. The result of the leave-one-out internal validation was R_CV²=0.865 7, the results of the three-fold internal validation were R_training²=0.879 3, R_test²=0.882 4, and the result of external validation was R_ext²=0.946 7. These results indicated that the best QSAR model exhibited good stability and predictability. Analysis of the modeling descriptors indicated that the descriptors related to hydrogen bond donors in the molecular structure of citral-based derivatives had a significant effect on antifungal activity against C. gloeosporioides. This study can provide theoretical guidance for the design of citral-based derivatives with better antifungal activity against C. gloeosporioides.

Key words: citral, derivatives, quantitative structure-activity relationship (QSAR), heuristic regression

中图分类号:

TQ35

曾嵘, 司红燕, 陈尚钘, 宋杰, 王宗德, 廖圣良. 柠檬醛基抗油茶炭疽病菌衍生物的定量构效关系研究[J]. 生物质化学工程, 2021, 55(1): 49-55.

Rong ZENG, Hongyan SI, Shangxing CHEN, Jie SONG, Zongde WANG, Shengliang LIAO. Quantitative Structure-activity Relationship Analysis of Citral-based Antifungal Derivatives Against Colletotrichum gloeosporioides[J]. Biomass Chemical Engineering, 2021, 55(1): 49-55.

图/表 7

表1

化合物的信息[19-20]"

序号 ID	化合物名称 name	化学式 formula	IC₅₀	lg(IC₅₀)
1	橙花醇 (Z)-3, 7-dimethylocta-2, 6-dien-1-ol		12.9800	1.1133
2	四氢香叶醇 3, 7-dimethyloctan-1-ol		13.1200	1.1179
3	橙花素 methyl (E)-2-((7-hydroxy-3, 7-dimethyloctylidene)amino)benzoate		14.100	1.1492
4	香叶醇 (E)-3, 7-dimethylocta-2, 6-dien-1-ol		21.5400	1.3332
5	鸢尾酮 (E)-4-(2, 5, 6, 6-tetramethylcyclohex-2-en-1-yl)but-3-en-2-one		46.2600	1.6652
6	异戊酸香叶酯 (E)-3, 7-dimethylocta-2, 6-dien-1-yl 3-methylbutanoate		69.8100	1.8439
7	香茅醛肟 (E)-3, 7-dimethyloct-6-enal oxime		76.5226	1.8838
8	异丁酸橙花酯 (Z)-3, 7-dimethylocta-2, 6-dien-1-yl isobutyrate		109.6000	2.0398
9	柠檬醛肟 (1E, 2E)-3, 7-dimethylocta-2, 6-dienal oxime		169.0892	2.2281
10	乙酸橙花酯 (Z)-3, 7-dimethylocta-2, 6-dien-1-yl acetate		173.6900	2.2348
11	柠檬醛 (E)-3, 7-dimethylocta-2, 6-dienal		316.3100	2.5001
12	异丁酸香叶酯 (E)-3, 7-dimethylocta-2, 6-dien-1-yl isobutyrate		497.2700	2.6966
13	β-紫罗兰酮 (E)-4-(2, 6, 6-trimethylcyclohex-1-en-1-yl)but-3-en-2-one		596.6900	2.7757
14	丁酸香叶酯 (E)-3, 7-dimethylocta-2, 6-dien-1-yl butyrate		1042.6400	3.0181
15	香茅醛乙二缩醛 2-(2, 6-dimethylhept-5-en-1-yl)-1, 3-dioxolane		1215.4100	3.0847
16	丙酸香叶酯 (E)-3, 7-dimethylocta-2, 6-dien-1-yl propionate		1377.7900	3.1392
17	甲酸香叶酯 (E)-3, 7-dimethylocta-2, 6-dien-1-yl formate		3710.9500	3.5695
18	柠檬腈 (E)-3, 7-dimethylocta-2, 6-dienenitrile		5064.8900	3.7046
19	柠檬醛乙二醇缩醛 (E)-2-(2, 6-dimethylhepta-1, 5-dien-1-yl)-1, 3-dioxolane		5953.6700	3.7748
20	甲基紫罗兰酮 (E)-1-(2, 6, 6-trimethylcyclohex-2-en-1-yl)pent-1-en-3-one		10455.1800	4.0193
21	香茅醛 3, 7-dimethyloct-6-enal		10884.7600	4.0368
22	橙花叔醇 (Z)-3, 7, 11-trimethyldodeca-1, 6, 10-trien-3-ol		21.2100	1.3265
23	乙酸香叶酯 (E)-3, 7-dimethylocta-2, 6-dien-1-yl propionate		14540.4600	4.1626
24	香茅醛1, 2-丙二醇缩醛 4-methyl-2-(6-methylhept-5-en-2-yl)-1, 3-dioxolane		20477.4400	4.3113
25	香茅醛二乙缩醛 8, 8-diethoxy-2, 6-dimethyloct-2-ene		5501800.8400	6.7405
26	羟基香茅醛 7-hydroxy-3, 7-dimethyloctanal		302182.4500	5.4803

表1

表2

表3

表4

表5

图1

图2

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描述符数量/个 number of descriptors	R²	△R²=R_k²-R_k-1²	R_CV²
1	0.6416		0.5878
2	0.8093	0.1677	0.7578
3	0.8811	0.0718	0.8358
4	0.9265	0.0454	0.8657
5	0.9540	0.0275	0.9185
6	0.9694	0.0154	0.9359

描述符序号 descriptor No.	回归系数 regression coefficients	回归系数误差 regression coefficient error	t检验值 t-test	描述符 name of desciptor
0	-0.2517	2.0070	-0.1254	截距intercept
X₁	6.0769	0.5577	10.8958	氢原子之间的相互斥力Min e-e repulsion for a H atom
X₂	-75.3810	11.0750	-6.8066	分子中带正电荷加权部分表面积比例 ESP-FPSA-3 Fractional PPSA(PPSA-3/TMSA)
X₃	-0.1498	0.0298	-5.0328	氢原子的数量number of H atoms
X₄	0.3072	0.0880	3.4912	分子表面正电荷分布以及分子总表面积 WPSA-3 Weighted PPSA(PPSA-3^*TMSA/1000)

训练集 training set	样本个数 samples No.	R_training²	F	S²
A+B	14	0.7936	21.15	0.2314
A+C	14	0.8871	26.18	0.1397
B+C	14	0.9573	50.44	0.0610
平均值average		0.8793	32.59	0.1440
C	7	0.8707	13.47	0.2037
B	7	0.8523	11.54	0.2404
A	7	0.9244	24.47	0.1062
平均值average		0.8824	16.49	0.1834

序号 No.	预测值 predicted	实验值 experimental	差值 D-value
22	1.1975	1.3265	-0.1290
23	4.0527	4.1626	-0.1099
24	5.0130	4.3113	0.7017
25	6.1679	6.7405	-0.5726
26	5.5900	5.4803	0.1097

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