Synthesis, antifungal activity and SAR of N-substituted and N,N-disubstituted 2,4-dihydroxythiobenzamides

Abstract

Various structural types of amides are characterized by fungicidal activity. Many of them have been widely used for controlling plant diseases caused by Rhizoctonia, Corticium, Typhula, Gymnosporangium, Botrytis and Phytophthora. [1][2][3][4][5][6][7][8] Various structural modifications based on structure-activity studies have been undertaken to obtain compounds of greater efficacy. 2,3,5) Our research involves sulphur analogues of amidesthioamides. A wide spectrum of fungistatic activity has been confirmed for this group of compounds. They possess inhibitory activity against moulds, 9) yeasts, 10) dermatophytes 11) and phytopathogenic fungi in vitro. 12,13) Fungistatic effects "in vivo" on Erysiphe graminis were also reported. 13)Therefore we decided to continue our research in this field. This paper presents the synthesis and biological activity of N-and N,N-substituted 2,4-dihydroxythiobenzamides. The experiments were carried out in vitro using five strains of phytopathogenic fungi. Taking into account parameters of lipophilicity (calculated n-octanol-water partition coefficient and log k w obtained from reversed phase chromatography) and the electronic properties (characteristic bands of 1 H NMR, MS and IR spectra) connected with the influence of N-substitution on the thiocarbamoyl moiety, structure-activity relationships were also examined. Materials and Methods Analytical methodsMelting point measurements were made using a Boetius apparatus. Elemental analyses were performed to determine C, H and N contents (Perkin-Elmer 2400 analyser). The results of analyses (C, N, H) were withinϮ0.4% of the theoretical values. 1 H NMR spectra were recorded using a Varian 200 or a Bruker 500 spectrometer, standard TMS, and solutions in DMSO-d 6 , shift d (ppm). The spectra were interpreted with reference to the proton connected with heteroatoms and aliphatic carbon atom. Oscillation spectra were recorded with a Perkin-Elmer FT-IR 1725X spectrophotometer (in KBr) in the range of 600-4000 cm Ϫ1 . The EIMS spectra (70 eV) were recorded using a AMD-604 spectrometer. The spectrum of compound 10 was taken by means of the ionisation method LSIMA (NaOAc/MeOH) using the resolving power HR forHPLC was carried out using a liquid chromatograph (Knauer) with a dual pump, a 20 ml simple injection valve and a UV-visible detector (254, 320 nm). The Hypersil BDS C18 (5mm, 150ϫ4.6 mm) column was used as the stationary phase. The samples were prepared as solutions in methanol. University, pl. M.C. Skl ⁄ odowska 3, 20-031 Lublin, Poland (Received March 14, 2005; Accepted September 14, 2005) N-Substituted and N,N-disubstituted 2,4-dihydroxythiobenzamides were synthesized and their fungistatic properties were examined. The compounds were prepared by reacting sulfinyl-bis-(2,4-dihydroxythiobenzoyl) with primary or secondary amines. The activities of the derivatives against five phytopathogenic fungi were measured in vitro. The growth-inhibitory activity of these compounds depends mainly on their lipophilicity. Parabolic relationships bet...

Synthesis and antifungal activity of novel 5‐substituted 4‐(1,3,4‐thiadiazol‐2‐yl)benzene‐1,3‐diols

“…The compounds under consideration show moderate fungicidal effect contrary to various heterocyclic derivatives with 2,4-dihydroxyphenyl moiety described previously [22,23].…”

“…In our previous work, many heterocyclic compounds containing 2,4-dihydroxyphenyl moiety were reported with good fungicidal, antibacterial, and antitumor activities [22][23][24]. This substituent seems to be crucial in the biological effects.…”

“…The incorporation of dihydroxyphenyl moiety in organic compounds, not limited to 1,3,4-thiadiazole has attracted considerable attention due to its naturally derived characterization and wide prevalence in pesticides and medicinal compounds. In our previous work, many heterocyclic compounds containing 2,4-dihydroxyphenyl moiety were reported with good fungicidal, antibacterial, and antitumor activities [22][23][24]. This substituent seems to be crucial in the biological effects.…”

Xanthane Hydride

“…49 The synthesized thiobenzamide has been tested for antifungal activity. Amidation of xanthane dihydride with various carboxylic acid derivatives in the presence of either DIC (N,N -diisopropylcarbodiimide) or DCC (dicyclohexylcarbodiimide) was reported.…”

The structure–bioavailability approach in antifungal agents

“…Usually, the lipophilic properties of these compounds are being described on the base of the calculated log P [23][24][25]. However, available theoretical models in log P calculation do not consider the structure of studied molecules.…”