19种常见中药材醇提物的体外抗菌活性筛选

为考察19种中药材乙醇提取物的体外抗临床常见致病菌的活性,该文将中药粗粉用80%乙醇浸泡提取,提取液减压浓缩制备成浸膏,采用琼脂打孔法测定提取物抑菌圈,通过微量倍比稀释法测定最低抑菌浓度(MIC)和最低杀菌浓度(MBC/MFC)。结果表明:所筛选的19种中药材乙醇提取物对不同的菌株具有不同程度的抑制作用,14种中药材乙醇提取物抗SA、EC、PA和CA的抑菌圈范围在8～27 mm之间,其中地锦草、四块瓦、三颗针、马尾黄连和土大黄的提取物抗SA、EC的抑菌圈范围在10.3～26.6 mm之间。马尾黄连、孜然、地锦草、广西莪术、穿心莲、益母草、吴茱萸、土大黄、叶上花、土连翘、凤尾草和三颗针的醇提物对MRSA和铜绿假单胞菌耐药菌均具有显著的抗微生物活性,其MIC/MBC值在391～6 250μg·m L^-1之间;地锦草、三颗针抗MRSA的最低MIC值分别为391、781μg·m L^-1,抗PA耐药菌的最低MIC值均为1 562.5μg·m L^-1;马尾黄连、孜然和三颗针的醇提物对白色念珠菌耐药菌有中等抑制作用,杀菌效果不明显。该...     

Microwave assisted one pot synthesis of some novel 2,5-disubstituted 1,3,4-oxadiazoles as antifungal agents

Sodium bisulfite has been reported first time for the synthesis of 2,5-disubstituted 1,3,4-oxadiazole using microwave and conventional method in ethanol-water. The yields obtained are in the range of 90-95% using microwave and 87-91% using conventional method. All the synthesized compounds (8a-8s) are novel and were evaluated for their in vitro antifungal activity. SAR for the series has been developed by comparing their MIC values with miconazole and fluconazole. Some of the compounds from the series like 8k was equipotent with miconazole against Candida albicans and Fusarium oxysporum. Also compound 8n was equipotent with miconazole against F. oxysporum.     

Promising antifungal agents: A minireview

In the recent past, prevalence of life threatening fungal diseases have increased rapidly in immune-compromised cases such as acquired immunodeficiency syndrome (AIDS), cancer, organ transplant etc. Side by side, the appearance of drug resistance to the presently available antifungal therapeutics is on a rapid rise. It has become a top priority for the academia and pharmaceutical industries to develop new antifungal agents able to combat this resistance, and at the same time, possess potential broad spectrum of activity and minimum toxicity. An understanding of the pharmacological interactions between antifungal agents and their targets offers opportunities for design of new therapeutics. This review discusses the various methodology of drug design, structure activity relationships (SARs), and mode of action of variety of new antifungal agents.     

Green synthesis and structural classification of Acacia nilotica mediated-silver doped titanium oxide (Ag/TiO2) spherical nanoparticles: Assessment of its antimicrobial and anticancer activity

Current exanimation reports, green fabrication of silver doped TiO₂ nanoparticles (Ag/TiO₂) using aqueous extract of Acacia nilotica as bio-reductant and assess its potential as antimicrobial and anticancer agent. The obtained spherical Ag/TiO₂ were characterized by various analytical techniques including FTIR, (XRD), (FE-SEM EDS), and (TEM). Synthesized Ag/TiO₂ demonstrated broad spectrum antibacterial and anticandidal activity. The order of antimicrobial activity was found to be E. coli > C. albicans > MRSA > P. aeruginosa. In addition, cytotoxicity and oxidative stress of Ag/TiO₂ nanoparticles in (MCF-7) cells was also investigated. Outcomes of MTT assay showed concentration dependent reduction in cell viability. Further, synthesized NPs reduced the level of glutathione, induced ROS generation and lipid peroxidation in the treated cells. Therefore, it is envisaged that these spherical nanoparticles may be exploited in drug delivery, pharmaceutical, and food industry.     

Novel pyrazole integrated 1,3,4-oxadiazoles: Synthesis,characterization and antimicrobial evaluation

A novel series of 2-(5-methyl-1,3-diphenyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4-oxadiazoles 7(a–m) were synthesized either by cyclization of N′-benzoyl-5-methyl-1,3-diphenyl-1H-pyrazole-4-carbohydrazide 4a using POCl₃ at 120 °C or by oxidative cyclization of hydrazones derived from various arylaldehyde and (E)-N′-benzylidene-5-methyl-1,3-diphenyl-1H-pyrazole-4-carbohydrazide 5(a–d) using chloramine-T as oxidant. Newly synthesized compounds were characterized by analytical and spectral (IR, ¹H NMR, ¹³C NMR and LC–MS) methods. The synthesized compounds were evaluated for their antimicrobial activity and were compared with standard drugs. The compounds demonstrated potent to weak antimicrobial activity. Among the synthesized compounds, compound 7m emerged as an effective antimicrobial agent, while compounds 7d, 7f, 7i and 7l showed good to moderate activity. The minimum inhibitory concentration of the compounds was in the range of 20–50 μg mL⁻¹ against bacteria and 25–55 μg mL⁻¹ against fungi. The title compounds represent a novel class of potent antimicrobial agents.     

Design,synthesis and SAR exploration of hybrid 4-chlorophenylthiazolyl-s-triazine as potential antimicrobial agents

Two novel series of hybrid class 4-chlorophenylthiazole-s-triazine were synthesized via nucleophilic substitution of 2,4,6-trichloro-1,3,5-triazine with distinguished alkenyl/alkyl/aryl/hetero alkyl–aryl amino and mercapto nucleophiles under nitrogen atmosphere. We identified that the spectrums of antibacterial activity of all tested compounds reveal promising and significant inhibition of gram-positive and gram-negative micro-organisms and the most active compounds, 31d and 32d, were found to be non-toxic in preliminary cytotoxicity assay. We also report that the Molinspiration and Osiris Property Explorer calculations have found a new lead 32d, which binds preferentially to the nuclear receptor to exhibit antibacterial potency.     

Aryl fluorosulfate analogues as potent antimicrobial agents: SAR,cytotoxicity and docking studies

A series of aryl fluorosulfate analogues (1–37) were synthesized and tested for in vitro antibacterial and antifungal studies, and validated by docking studies. The compounds 9, 12, 14, 19, 25, 26, 35, 36 and 37 exhibited superior antibacterial potency against tested bacterial strains, while compounds 2, 4, 5, 15, 35, 36 and 37 were found to have better antifungal activity against tested fungal strains, compared to standard antibiotic gentamicin and ketoconazole respectively. Among all the synthesized 37 analogs, compounds 25, 26, 35, 36 and 37 displayed excellent anti-biofilm property against Staphylococcus aureus. The structure–activity relationship (SAR) revealed that the antimicrobial activity depends upon the presence of –OSO₂F group and slender effect of different substituent’s on the phenyl rings. The electron donating (OCH₃) groups in analogs increase the antibacterial activity, and interestingly the electron withdrawing (Cl, NO₂, F and Br) groups increase the antifungal activity (except compound 35, 36 and 37). The mechanism of potent compounds showed membrane damage on bacteria confirmed by SEM. Compounds 35, 36 and 37 exhibited highest glide g-scores in molecular docking studies and validated the biocidal property.     

Supramolecular cobalt(II)-pyridine-2,5-dicarboxylate complexes with isonicotinamide, 2-amino-3-methylpyridine and 2-amino-6-methylpyridine: Syntheses, crystal structures, spectroscopic, thermal and antimicrobial activity studies

The mer-[Co(pydca)(H₂O)₃(ina)]·H₂O (1), (2a3mpyH)₂[Co(pydca)₂(H₂O)₂]·2H₂O (2) and (2a6mpyH)₂[Co(pydca)₂(H₂O)₂]·2H₂O (3) complexes (H₂pydca: pyridine-2,5-dicarboxylic acid, ina: isonicotinamide, 2a3mpy = 2-amino-3-methylpyridine and 2a6mpy = 2-amino-6-methylpyridine) were synthesised and characterised by elemental analysis, magnetic and spectroscopic measurements (UV-Vis and IR spectra) and single crystal X-ray diffraction technique. The thermal behaviour of the complexes was also studied by simultaneous thermal analysis techniques (TG, DTG and DTA). In complex 1, Co(II) ion was coordinated by one bidentate pydca, one isonicotinamide and three aqua ligands to generate a CoN₂O₄ distorted octahedral geometry. Complexes 2 and 3 crystallise in the triclinic system and space group and the structures consist of one complex anion [Co(pydca)₂(H₂O)₂]²⁻, two protonated aminomethylpyridinium cations, ampyH⁺ and two crystal water molecules. In the anions, the Co(II) ions have a distorted octahedral configuration and are coordinated by two bidentate pydca and two trans-aqua ligands. The pydca ligand is coordinated to the Co(II) by both the heterocyclic N atom and the adjacent carboxylate group O atom, creating a chelate ring, while protonated ampy ions behave as counter ion.     

Hydrazones of 2-aryl-quinoline-4-carboxylic acid hydrazides: synthesis and preliminary evaluation as antimicrobial agents

A new series of 2-arylquinoline-4-carboxylic acid hydrazide–hydrazones was synthesized using an appropriate synthetic route. All the target compounds were evaluated for their in vitro antimicrobial activity against Staphylococcus aureus as an example for Gram-positive bacteria, Escherichia coli as an example for Gram-negative bacteria, and Candida albicans as a representative of fungi. The minimum inhibitory concentration (MIC) was determined for test compounds as well as for reference standards. Among the compounds tested, compounds having nitro substituents at the arylidene moiety showed the most potent antifungal as well as antibacterial activities against E. coli. Compound 23 displayed an antifungal activity comparable to that of nystatin. However, none of the compounds demonstrated any antibacterial activity against S. aureus. Hydrophobicity of the target compounds correlated weakly with their antibacterial and antifungal activities. The most potent compounds namely, 7, 18, 19, 22, and 23 were assessed for hemolytic toxicity and found to be non-hemolytic up to a concentration of 100 μg/mL. In addition, the most potent compound (23) was evaluated for in vitro cytotoxic activity against various cancer cell lines. This compound was found to display no cytotoxic activity but rather it induces the proliferation rate of Hep-G2 cells.     

First example of Azo-Sulfa conjugated chromene moieties: Synthesis,characterization, antimicrobial assessment,docking simulation as potent class I histone deacetylase inhibitors and antitumor agents

This report presents the development of a novel and primary model of sulfonamide compounds encompassing a chromene azo motif with the intent of becoming applicable for drug candidates in the cases of drug-resistant pathogens. The novel molecules (7a–n) have been synthesized via a two-step reaction. First, 4-((2, 4-dihydroxyphenyl)diazenyl)benzenesulfonamide (3a–e) were obtained through the reaction of their corresponding diazotized 4-aminobenzenesulfonamides (1a–e) with resorcinol, followed by the heterocyclization of 3a–e with arylidenemalononitriles (6a–d). Upon structural identification, the newly synthesized compounds were evaluated for their antibacterial and antifungal activities. Moreover, their cytotoxic screening was performed against three cancer cell lines: HCT-116, HepG-2, and MCF-7. Further examinations were comprised of the inhibitory effect analyses of the novel sulfonamide/chromene derivatives against the HDAC classes and the Tubulin polymerization in order to discern the prime antitumor drug candidates.     

Design,synthesis and evaluation of antimicrobial activity of N-terminal modified Leucocin A analogues

Class IIa bacteriocins are potent antimicrobial peptides produced by lactic acid bacteria to destroy competing microorganisms. The N-terminal domain of these peptides consists of a conserved YGNGV sequence and a disulphide bond. The YGNGV motif is essential for activity, whereas, the two cysteines involved in the disulphide bond can be replaced with hydrophobic residues. The C-terminal region has variable sequences, and folds into a conserved amphipathic α-helical structure. To elucidate the structure–activity relationship in the N-terminal domain of these peptides, three analogues (1–3) of a class IIa bacteriocin, Leucocin A (LeuA), were designed and synthesized by replacing the N-terminal β-sheet residues of the native peptide with shorter β-turn motifs. Such replacement abolished the antibacterial activity in the analogues, however, analogue 1 was able to competitively inhibit the activity of native LeuA. Native LeuA (37-mer) was synthesized using native chemical ligation method in high yield. Solution conformation study using circular dichroism spectroscopy and molecular dynamics simulations suggested that the C-terminal region of analogue 1 adopts helical folding as found in LeuA, while the N-terminal region did not fold into β-sheet conformation. These structure–activity studies highlight the role of proper folding and complete sequence in the activity of class IIa bacteriocins.     

Design,synthesis and molecular modeling studies of new series of s-triazine derivatives as antimicrobial agents against multi-drug resistant clinical isolates

Three novel series of s-triazine derivatives, including thirty-five new compounds 2a-d, 3a-3p, 4b-d, 5b-d, 6d-6d, and 7a-7f were synthesized comprising a diversity of substituents based on the structure of Astrazeneca arylaminotriazine DNA gyrase B inhibitor. The antimicrobial activity was determined for all compounds against Staphylococcus aureus, Escherichia coli and Candida albicans using the two-fold serial dilution technique and against reference standards Ampicillin for the antibacterial screening and Clotrimazole regarding the antifungal evaluation. The tested compounds showed strong to moderate antibacterial inhibitory action and weak antifungal activity. Compounds 3j and 6b were the most potent antibacterial agents against the tested strains and multi-drug resistant (MDR) clinical isolates of Klebsiella pneumoniae and methicillin resistant Staphylococcus aureus (MRSA1) with minimal toxicity in comparison to the reference drugs. In silico molecular properties calculations and molecular docking study for 3j and 6b revealed that both compounds could be considered as promising antibacterial DNA gyrase B inhibitors.     

Green synthesis-assisted copper nanoparticles using Aegle marmelos leaves extract: physical,optical, and antimicrobial properties

In the present report, Aegle marmelos leaf powder was used to synthesize copper nanoparticles (CuNPs) using a simple and cost-effective method. A. marmelos leaves have various medicinal uses including for the treatment of diarrhoea, constipation, diabetes, cholera, skin diseases, earache, blood purification, heart problems, and so on. The plant biomolecules induce the reduction of Cu²⁺ ions to CuNPs and also act as a capping and stabilizing agent. The formation of CuNPs was confirmed using photoluminescence (PL) excitation and emission spectra on a Shimadzu RF-5301 PC spectrofluorophotometer and the absorbance spectra of a UV–visible spectrophotometer at different stages during the synthesis process. In addition, other properties of synthesized CuNPs were also investigated using X-ray diffraction, Fourier transform infrared spectroscopy, and transmission electron microscopy techniques. The average size of the synthesized CuNPs was in the range 20–40 nm. Furthermore, the synthesized NPs were also considered for an antimicrobial study against Gram-positive Staphylococcus aureus and Proteus, and Gram-negative Escherichia coli and Salmonella spp. using the agar well diffusion method. The zone of inhibition against the Gram-positive bacteria was greater than the zone of inhibition against the Gram-negative bacteria. These investigation results suggest that synthesized NPs are promising nanomaterials for use as antimicrobial agents.     

One pot three components microwave assisted and conventional synthesis of new 3-(4-chloro-2-hydroxyphenyl)-2-(substituted) thiazolidin-4-one as antimicrobial agents

A one-pot, three-component, microwave assisted and conventional synthesis of new 3-(4-chloro-2-hydroxyphenyl)-2-(substituted) thiazolidin-4-one (4a–n) was carried out by using N,N-dimethylformamide as a solvent with high product yield. Among these synthesized compounds (4f, 4g, 4l and 4m) were found to be a broad spectrum molecule active against all bacterial and fungus strains tested, except fungus Aspergillus niger. Amongst the compounds (4g, 4l and 4m) were found to be more potent than respective standard drugs used in the experiment against Candida albicans, Staphylococcus aureus and Aspergillus flavus, respectively. All synthesized compounds were also tested for their cytotoxic activity against HeLa and MCF-7 cell lines by the sulforhodamine B (SRB) assay. This study shows that all compounds were non-cytotoxic in nature, and confirmed their antimicrobial specificity apart from any general cytotoxicity.     

Antimicrobial and cytotoxic activity of 18 prenylated flavonoids isolated from medicinal plants: Morus alba L., Morus mongolica Schneider, Broussnetia papyrifera (L.) Vent, Sophora flavescens Ait and Echinosophora koreensis Nakai

Antimicrobial activity of the 18 prenylated flavonoids, which were purified from five different medicinal plants, was evaluated by determination of MIC using the broth microdilution methods against four bacterial and two fungal microorganisms (Candida albicans, Saccaromyces cerevisiae, Escherichia coli, Salmonella typhimurium, Staphylococcus epidermis and S. aureus). Papyriflavonol A, kuraridin, sophoraflavanone D and sophoraisoflavanone A exhibited a good antifungal activity with strong antibacterial activity. Kuwanon C, mulberrofuran G, albanol B, kenusanone A and sophoraflavanone G showed strong antibacterial activity with 5–30 μg/ml of MICs. Morusin, sanggenon B and D, kazinol B, kurarinone, kenusanone C and isosophoranone were effective to only gram positive bacteria, and broussochalcone A was effective to C. albicans. IC₅₀ values of papyriflavonol A, kuraridin, sophoraflavanone D, sophoraisoflavanone A and broussochalcone A in HepG2 cells were 20.9, 37.8, 39.1, 22.1, and 22.0 μg/ml, respectively. These results support the use of prenylated flavonoids in Asian traditional medicine to treat microbial infection and indicate a high potential for prenylated flavonoids as antimicrobial agents as well as anti-inflammatory agents.     

Screening and identification of actinobacteria from marine sediments: Investigation of potential producers for antimicrobial agents and type I polyketides

Marine actinobacteria were isolated from the sediment samples collected in Xinghai Bay, Xiaoping Island and Changhai in Dalian, China. Fifteen selective media were employed, of which Humic acid-Vitamin medium recovered the highest number of isolates. Eleven of the 239 isolates obtained from the selective media were selected for further investigations based on colony morphology and pigment formation. Phylogenetic analysis of their 16S rRNA sequences showed that these strains belong to the genera of Streptomyces and Micromonospora. One of these strains identified is a new species of Streptomyces. Type I polyketide synthase (PKSI) gene fragments were amplified from three strains. The PKSI sequence of one of these strains (S187) showed high homology to the KS gene involved in meridamycin biosynthesis. Based on this result, the neurotrophic activity of S187 was further investigated. Culture broth of S187 was applied to rat pheochromocytoma (PC12) cells, and a 2.3-fold increase in growth over control cells was observed by the 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide assay. These results indicated the importance of further exploration of the marine actinobacteria in Dalian sea area for antimicrobial agents and type I polyketides.     

Synthesis, iron(III)-binding affinity and in vitro evaluation of 3-hydroxypyridin-4-one hexadentate ligands as potential antimicrobial agents

Iron is a critical element for the survival of bacteria. We have designed and synthesized two novel 3-hydroxypyridin-4-one hexadentate ligands with high affinity for iron(III), which disrupt bacterial iron absorption. Biological studies demonstrate that these two chelators have significant inhibitory effect against both Gram-positive and Gram-negative bacteria, and therefore have potential as antimicrobial agents.     

Synthesis, spectral (UV-Vis, IR, ESI-MS), magnetic and structural characterizations, and the antimicrobial effect of potassium isothiocyanato-(N-salicylidene-amino-acidato)cuprates

A series of potassium isothiocyanato-(N-salicylidene-amino acidato)cuprates with the general formulas of K₂[Cu₂(sal-aa)₂(μ-NCS)₂]·nH₂O, where n = 0 or 4 and (sal-aa) stands for the dianion of N-salicylideneamino acid derived from glycine (I), dl-α-alanine (II), dl-valine (III), dl-phenylalanine (IV), and {K[Cu(sal-β-ala)(μ-NCS)]}_n for β-alanine (V), respectively, was synthesized and fully characterized by elemental analysis, UV-Vis and IR spectroscopy, ESI-MS spectrometry, magnetic measurements, and X-ray structural analysis (II and IV). It has been found that the copper(II) atom adopts a distorted square-pyramidal surrounding in the dimeric complexes I-IV, while the geometry in the polymeric complex V can be described as distorted square-bipyramidal. The analysis of magnetic properties revealed weak antiferromagnetic exchanges in the dinuclear species I-IV and an alternating ferro/antiferromagnetic exchange in the case of 1D-polymeric compound V. Moreover, the complexes were tested for their antibacterial activity against the G+ bacteria Staphylococcus aureus, G− bacteria Escherichia coli, filamentous fungi Microsporum gypseum, and yeast Candida albicans. The best results were achieved with G+ bacteria S. aureus with MIC values in the range of 0.22-0.57 mmol L⁻¹. It may be concluded that both the antimicrobial and antifungal activity decreased within the tested group of cuprates derived from α-amino acids with the increasing lipophility of the complexes, i.e.I → IV.     

Palladium(II) complexes of quinolinylaminophosphonates: synthesis, structural characterization, antitumor and antimicrobial activity

Three types of palladium(II) halide complexes of quinolinylaminophosphonates have been synthesized and studied. Diethyl and dibutyl [α-anilino-(quinolin-2-ylmethyl)]phosphonates (L1, L2) act as N,N-chelate ligands through the quinoline and aniline nitrogens giving complexes cis-[Pd(L1/L2)X₂] (X═Cl, Br) (1-4). Their 3-substituted analogues [α-anilino-(quinolin-3-ylmethyl)]phosphonates (L3, L4) form dihalidopalladium complexes trans-[Pd(L3/L4)₂X₂] (5-8), with trans N-bonded ligand molecules only through the quinoline nitrogen. Dialkyl [α-(quinolin-3-ylamino)-N-benzyl]phosphonates (L5, L6) give tetrahalidodipalladium complexes [Pd₂(L5/L6)₃X₄] (9-12), containing one bridging and two terminal ligand molecules. The bridging molecule is bonded to the both palladium atoms, one through the quinoline and the other through the aminoquinoline nitrogen, whereas terminal ligand molecules are coordinated each only to one palladium via the quinoline nitrogen. Each palladium ion is also bonded to two halide ions in a trans square-planar fashion. The new complexes were identified and characterized by elemental analyses and by IR, UV-visible, ¹H, ¹³C and ³¹P nuclear magnetic resonance and ESI-mass spectroscopic studies. The crystal structures of complexes 1-4 and 6 were determined by X-ray structure analysis. The antitumor activity of complexes in vitro was investigated on several human tumor cell lines and the highest activity with cell growth inhibitory effects in the low micromolar range was observed for dipalladium complexes 11 and 12 derived from dibutyl ester L6. The antimicrobial properties in vitro of ligands and their complexes were studied using a wide spectrum of bacterial and fungal strains. No specific activity was noted. Only ligands L3 and L4 and tetrahalidodipalladium complexes 9 and 11 show poor activities against some Gram positive bacteria.