Syntheses and Biological Activities of Novel Imine and Imide Derivatives Bearing 1,2,4-Triazole Moiety†

doi:10.7503/cjcu20130543

Abstract

Abstract:

According to active groups combination principle, a series of novel imine and imide derivatives bearing 1,2,4-triazole moiety was designed and synthesized. The key intermediate 3-substituted phenyl-4-amino-1,2,4-triazole-5-thiones was synthesized by esterification, hydrazinolysis, salt and cyclization reactions, and then was condensed with aromatic aldehydes and isobenzofuran-1,3-dione to obtain imine and imide derivatives, which were subjected to the thioetherification with suitable halides(RX) to produce the corresponding 24 novel imine and imide derivatives bearing 1,2,4-triazole moiety. The structures of target compounds were fully characterized by ¹H NMR, IR, mass spectroscopy and elemental analysis. The preliminary bioassay results showed that most of the compounds possessed certain fungicidal activities. At the concentration of 150 mg/L, the inhibition rates of compounds 9a, 9d and 9e against Rhizoctonia solani were very similar with the commercial fungicide Flusilazole. Meanwhile, the preliminary structure-activity relationships(SAR) were discussed in order to investigate the essential structures required for their bioactivities. In addition, their in vitro antitumor activities were evaluated against three cancer cell lines[human alveolar epithelial cells(A549), human breast cancer cells(MD-MBA-231) and human prostate cancer cells(PC-3M)] by the methyl thiazolyl tetrazolium(MTT) chromatometry method with Fluorouracil as a positive contrast drug. The bioassay data indicated that compounds 7c, 7f and 9k showed similar antiproliferation with Fluorouracil against A549 cell lines with IC₅₀ values of 38.3, 44.6 and 36.7 μmol/L, respectively. Most interestingly, compound 9k also exhibited a broad spectrum of antitumor activity against MCF-7 and MKN45 with IC₅₀ values of 147.5 and 60.7 μmol/L, respectively.

Key words: 1,2,4-Triazole, Fungicidal activity, Antitumor activity

CLC Number:

O625

TrendMD:

YANG Haikui, XU Wanfu, DUAN Anna, YOU Wenwei, ZHAO Peiliang. Syntheses and Biological Activities of Novel Imine and Imide Derivatives Bearing 1,2,4-Triazole Moiety^†[J]. Chem. J. Chinese Universities, 2014, 35(3): 555.

Figures/Tables 3

Scheme 1 Synthetic routes of the title compounds7a: R1=H, R2=4-FC6H4CH2; 7b: R1=H, R2=CH≡≡CCH2; 7c: R1=H, R2=4-ClC6H4COCH2; 7d: R1=H, R2=C6H5CH2; 7e: R1=H, R2=Me; 7f: R1=H, R2=4-Me C6H4COCH2; 9a: R1=H, R2=C6H5, R3=Me; 9b: R1=H, R2=C6H5, R3=C6H5CH2; 9c: R1=H, R2=C6H5, R3=CH2C=CH2; 9d: R1=H, R2=C6H5, R3=4-FC6H4CH2; 9e: R1=H, R2=C6H5, R3=CH≡≡CCH2; 9f: R1=3,4,5-(MeO)3, R2=3,4,5-(MeO)3C6H2, R3=Me; 9g: R1=3,4,5-(MeO)3, R2=3,4,5-(MeO)3C6H2, R3=CH2C=CH2; 9h: R1=3,4,5-(MeO)3, R2=3,4,5-(MeO)3C6H2, R3=CH≡≡CCH2; 9i: R1=3,4,5-(MeO)3, R2=3,4,5-(MeO)3C6H2, R3=4-FC6H4CH2; 9j: R1=3,4,5-(MeO)3, R2=3,4,5-(MeO)3C6H2, R3=2-ClC6H4CH2; 9k: R1=3,4,5-(MeO)3, R2=3,4,5-(MeO)3C6H2, R3=4-ClC6H4COCH2; 9l: R1=3,4,5-(MeO)3, R2=3,4,5-(MeO)3C6H2, R3=C6H5CH2; 9m: R1=3,4,5-(MeO)3, R2=4-FC6H4, R3=Me; 9n: R1=3,4,5-(MeO)3, R2=4-FC6H4, R3=C6H5CH2; 9o: R1=3,4,5-(MeO)3, R2=4-FC6H4, R3=2-ClC6H4CH2; 9p: R1=3,4,5-(MeO)3, R2=4-FC6H4, R3=4-FC6H4CH2; 9q: R1=3,4,5-(MeO)3, R2=4-FC6H4, R3=CH≡≡CCH2; 9r: R1=3,4,5-(MeO)3, R2=4-FC6H4, R3=CH2C=CH2.

Table 1 Fungicidal activities of compounds 7a—7f and 9a—9r*

Compd.	Inhibitory ratio(%)
Compd.	Fusarium oxysporum f.sp.cubense	Pestalotiopsis palmarum	Corynespora cmssiicola (Berk & Curt.)Wei	Colletotrichum gloeosporioides PenZ	Rhizoctonia solani
7a	++	-	-	-	+
7b	+	-	-	-	-
7c	-	-	-	-	+
7d	-	-	-	+	+
7e	+	-	-	-	-
7f	+	-	-	-	+
9a	++	+	+	+	++++
9b	-	-	-	-	++
9c	+	-	+	+	++
9d	++	++	-	+	++++
9e	+	-	+	+	++++
9f	-	-	-	-	+
9g	-	-	+	-	++
9h	-	-	-	+	++
9i	-	-	+	-	+
9j	-	+	-	-	+
9k	-	-	-	-	+
9l	-	-	-	++	++
9m	-	-	-	-	+
9n	-	+	-	-	++
9o	++	-	-	-	+
9p	-	-	+	-	++
9q	++	-	-	-	+
9r	-	-	+	-	++
Flusilazole	++++	++++	++++	+++	++++

Table 2 IC50 values of target compounds 7a—7f and 9a—9r against A549, MD-MBA-231 and PC-3M*

Compd.	IC₅₀/(μmol·L^-1)			Compd.	IC₅₀/(μmol·L^-1)
Compd.	A549		MD-MBA-231	PC-3M	A549	MD-MBA-231	PC-3M
7a	>200	>200	>200	9h	>200	>200	>200
7b	>200	>200	>200	9i	>200	>200	91.6
7c	38.3	>200	>200	9j	>200	>200	98.0
7d	>200	>200	>200	9k	36.7	147.5	60.7
7e	>200	>200	>200	9l	>200	>200	>200
7f	44.6	>200	>200	9m	>200	>200	>200
9a	>200	>200	34.1	9n	>200	89.6	>200
9b	>200	>200	97.9	9o	>200	>200	59.8
9c	>200	>200	>200	9p	>200	>200	>200
9d	104.6	59.8	>200	9q	>200	>200	61.3
9e	>200	>200	41.1	9r	>200	>200	>200
9f	>200	>200	99.2	5-Fu	35.4	14.2	22.6
9g	>200	>200	73.2

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