Biological Applications of Macrocyclic Schiff Base Ligands and Their Metal Complexes: A Survey of the Literature (2005–2019)

This article aims to provide a survey of biological applications of Schiff base macrocycles and their metal complexes, with emphasis given to the synthesis of the compounds and to their uses as antibacterial and antifungal agents. The literature on the subject, published during the 2005–2019 period, is shortly reviewed. This is an informed report collecting information on the addressed topic in a concise systematic way, and can be expected to be useful as a fast literature catalogue for researchers working on this and related domains.     

In Vitro Antifungal Activity and Mechanism of Ag3PW12O40 Composites against Candida Species

Fungal infections pose a serious threat to human health. Polyoxometalates (POMs) are metal–oxygen clusters with potential application in the control of microbial infections. Herein, the Ag₃PW₁₂O₄₀ composites have been synthesized and verified by Fourier transform infrared (FT-IR) spectrum, transmission electron microscopy (TEM), scanning electron microscope (SEM), elemental analysis, and X-ray diffraction (XRD). The antifungal activities of Ag₃PW₁₂O₄₀ were screened in 19 Candida species strains through the determination of minimum inhibitory concentration (MIC) by the microdilution checkerboard technique. The minimum inhibitory concentration (MIC₅₀) values of Ag₃PW₁₂O₄₀ are 2~32 μg/mL to the Candida species. The MIC₈₀ value of Ag₃PW₁₂O₄₀ to resistant clinical isolates C. albicans HL963 is 8 μg/mL, which is lower than the positive control, fluconazole (FLC). The mechanism against C. albicans HL963 results show that Ag₃PW₁₂O₄₀ can decrease the ergosterol content. The expressions of ERG1, ERG7, and ERG11, which impact on the synthesis of ergosterol, are all prominently upregulated by Ag₃PW₁₂O₄₀. It indicates that Ag₃PW₁₂O₄₀ is a candidate in the development of new antifungal agents.     

Biological activity of new amino phospha betaines with C10–C18 alkyl groups

New amino phospha betaines were obtained by quaternization of potassium salt of amino phosphonate and higher alkyl bromides. The structure of isopropyl (N-dodecyl-N,N- dimethylammoniomethyl)phosphonate was confirmed by single crystal X-ray diffraction. All synthesized compounds demonstrate high antibacterial and antifungal activities.     

Enhanced antifungal activities of four Zn(II) complexes based on uniconazole

Four Zn(II) complexes, [Zn L ₂(SO₄)]_n ( 1 ), [Zn L ₄(H₂O)₂]?2(NO₃)?4EtOH ( 2 ), [Zn L ₂Cl₂]? L ( 3 ), and [Zn L ₂Br₂]? L ( 4 ) ( L  = uniconazole), were synthesized using a hydrothermal method and characterized by elemental analysis, FT‐IR spectroscopy, and single‐crystal XRD. Complex 1 formed a one‐dimensional polymer chain. However, complexes 2 ‐ 4 were obtained as zero‐dimensional mononuclear coordination compounds. The antifungal activities of these complexes were then evaluated against four selected fungi using the mycelial growth rate method. The resulting data indicate that all complexes show better antifungal activities than their ligands and mixtures. In addition, the interactions between the metal salts of complexes 1 ‐ 4 and uniconazole seem to be synergistic. Furthermore, the polymer chain structure of complex 1 significantly enhanced the bioactivity, especially against Botryosphaeria ribis ( I ). Density functional theory (DFT) calculations were carried out to help explain the enhanced bioactivity after the formation of Zn(II) complexes. The resulting data show that the HOMO–LUMO energy gaps of complexes 1 ‐ 4 (0.0578, 0.0946, 0.1053, and 0.1245 eV) are smaller than that of the free ligand (0.1247 eV) and correlate with the antifungal activity of the zinc complexes.     

Synthesis,crystal structure and antifungal activity of a divalent cobalt(II) complex with uniconazole

Azole compounds have attracted commercial interest due to their high bactericidal and plant‐growth‐regulating activities. Uniconazole [or 1‐(4‐chlorophenyl)‐4,4‐dimethyl‐2‐(1H‐1,2,4‐triazol‐1‐yl)pent‐1‐en‐3‐ol] is a highly active 1,2,4‐triazole fungicide and plant‐growth regulator with low toxicity. The pharmacological and toxicological properties of many drugs are modified by the formation of their metal complexes. Therefore, there is much interest in exploiting the coordination chemistry of triazole pesticides and their potential application in agriculture. However, reports of complexes of uniconazole are rare. A new cobalt(II) complex of uniconazole, namely dichloridotetrakis[1‐(4‐chlorophenyl)‐4,4‐dimethyl‐2‐(1H‐1,2,4‐triazol‐1‐yl‐κN⁴)pent‐1‐en‐3‐ol]cobalt(II), [CoCl₂(C₁₅H₁₈ClN₃O)₄], was synthesized and structurally characterized by element analysis, IR spectrometry and X‐ray single‐crystal diffraction. The crystal structural analysis shows that the Co^II atom is located on the inversion centre and is coordinated by four uniconazole and two chloride ligands, forming a distorted octahedral geometry. The hydroxy groups of an uniconazole ligands of adjacent molecules form hydrogen bonds with the axial chloride ligands, resulting in one‐dimensional chains parallel to the a axis. The complex was analysed for its antifungal activity by the mycelial growth rate method. It was revealed that the antifungal effect of the title complex is more pronounced than the effect of fungicide uniconazole for Botryosphaeria ribis, Wheat gibberellic and Grape anthracnose.     

SYNTHESIS AND SPECTROSCOPIC STUDIES OF SOME FUNGITOXIC ORGANOLEAD(IV) COMPLEXES OF SULFUR AND NITROGEN DONOR LIGANDS

Abstract

Some organolead(IV) complexes derived from biologically active sulfur and nitrogen donor ligands have been synthesized and characterized by elemental analyses, molecular weight determinations and conductivity measurements. The trigonal bipyramidal and octahedral geometries for these complexes have been proposed on the basis of electronic, infrared and NMR (¹H and ¹³C) spectral evidences. The antifungal activity of some of the ligands and their complexes have also been evaluated against Fursarium oxysporum SCW. ex Frics f. sp. Ciceri (Pedwick) subram.     

The Synthesis and Biological Activities of [5-(4-Substituted Phenylsulfinyl/Sulfonyl)-1,3-Dimethyl-1H-Pyrazol-4-Yl]-Arylmethanones

Abstract

A novel series of pyrazole derivatives containing substituted phenylsulfinyl/sulfonyl group have been synthesized via the oxidation of intermediate pyrazole sulfoether with H₂O₂ in acetic acid. The novel compounds were characterized by melting point, ¹H NMR, FT-IR, MS, and elemental analysis or HRMS. The biological activity results showed that most of the title compounds exhibit significant fungicidal activities against Alternaria solani Sorauer, Phytophthora capsici, and Corynespora cassiicola.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text and figures.]     

Two New 4‐Hydroxyisoflavanes from the Root of Codonopsis cordifolioidea and Their Anti‐virus Activities

Two new 4‐hydroxyisoflavanes, cordifoliflavanes A and B (1 and 2), were isolated from the roots of Codonopsis cordifolioidea. Their structures were elucidated by spectroscopic methods, including extensive 1D‐ and 2D‐NMR techniques. Compounds 1 and 2 were tested for their anti‐HIV‐1 activities and anti‐tobacco mosaic virus activities. The results showed that compounds 1 and 2 have modest anti‐HIV‐1 activities and anti‐tobacco mosaic virus activities, respectively.     

One-Pot Synthesis and Fungicidal Activities of Derivatives of Imidazo [2,1-b]-1,3,4-thiadiazol-5(6H)-one

The isothiocyanates 2, obtained from aza-Wittig reactions of vinyliminophosphoranes 1 with CS ₂ , reacted with hydrazine to give 3-amino-2-thioxo-4-imidazolidinones 4. One-pot reactions of 4, aromatic isocyanates, Ph ₃ P, C ₂ Cl ₆ , and Et ₃ N generated imidazo[2,1-b]-1,3,4-thiadiazol-5(6H)-ones 7. Compound 7 exhibited good fungicidal activities, especially against Sclerotinia sclerotiorum de Bary and Botrytis Cinerea Pers.     

An Efficient Synthesis of New Substituted Spiro Pyrazolethieno,Pyrimidinethieno, and Benzodiazepinethieno Pyridazine Derivatives with Biological Activities

3-Ethyl 2-amino-4-methyl-5-phenyl thiophene carboxylate 1 was used as a starting material to synthesize 2a,b via coupling with malononitrile or acetyl acetone, respectively. When heated, under reflux in sodium ethoxide solution, 2a,b give 3a,b. On the other hand, when compounds 3a,b were heated under reflux in ethanol with hydrazine hydrate, thiourea, or 1,1-phenylenediamine hydrochloride and a catalytic amount of piperidine 4a,b, 5a,b and 6a,b, were produced, respectively. The new compounds were tested for their antimicrobial activity. Compounds 2a–6b showed antibacterial activities, and 2a,2b and 4b showed antifungal activities.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.