Studies on hydrazone derivatives as antifungal agents

The increasing clinical importance of drug-resistant fungal pathogens has urged additional need to fungal research and new antifungal compound development. For this purpose, some N-(1-benzyl-2-phenylethylidene)-N′-[4-(aryl)thiazol-2-yl]hydrazone (1a-e) and N-(1-phenylbutylidene)-N′-[4-(aryl)thiazol-2-yl]hydrazone (2a-e) derivatives were synthesised and evaluated for antifungal activity. Their antifungal activities against standard and clinical strands of Candida albicans, Candida glabrata, Candida utilis, Candida tropicalis, Candida krusei, Candida zeylanoides, and Candida parapsilosis were investigated. A significant level of activity was observed.     

Antimicrobial activities of some synthetic butenolides and their pyrrolone derivatives

In the present investigation, 17 new synthetic butenolides, i.e. 2-arylidene-4-(4-chloro/ethyl-phenyl)but-3-en-4-olides (3–19) have been synthesized from 3-(4-chloro-benzoyl)propionic acid or 3-(4-ethyl-benzoyl)propionic acid using appropriate reagents. Some of the selected butenolides were reacted with ammonia and benzylamine to give the corresponding pyrrolones (20–31) and N-benzyl-pyrrolones (32–39) respectively. All the compounds were screened for their antibacterial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa and antifungal activity against Candida albicans, Aspergillus niger, and Rhizopus oryza. Minimum inhibitory concentration (MIC) values of the compounds are reported. The pyrrolone derivatives discovered in this study may provide valuable therapeutic intervention for the treatment of microbial diseases, especially against fungal species.     

Synthesis,anti-inflammatory,analgesic, COX-1/2 inhibition activities and molecular docking study of pyrazoline derivatives

Design, synthesis and pharmacological activities of a group of 1,3,5-trisubstituted pyrazolines were reported. The chemical structures of the synthesized compounds have been assigned on the basis of IR, MS, ¹H NMR, and ¹³C NMR spectral analyses. The synthesized 1,3,5-trisubstituted pyrazoline derivatives were evaluated in vivo for anti-inflammatory, analgesic activities and in vitro for COX-1/2 inhibition assay. Among the tested compounds, derivatives 4h, 6e, 7a, 7e, and 9 showed more potent anti-inflammatory and analgesic activities than the reference drug celecoxib. On the basis of their higher activities in the in vivo studies compared with celecoxib, the five compounds 4h, 6e, 7a, 7e and 9 were selected to test their inhibitory activities against ovine COX-1/2 using an in vitro cyclooxygenase inhibition assay. Docking study of compounds 7a, 7e and 9 into the COX-2 binding site revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.     

Synthesis of reduced xanthatin derivatives and in vitro evaluation of their antifungal activity

The synthesis of new xanthanolide derivatives is reported starting from xanthatin, a sesquiterpenic lactone isolated from Xanthium macrocarpum (Asteraceae). In vitro evaluation of their antifungal activity has been investigated.     

米诺环素对临床几种常见假丝酵母菌体外药敏的初步探究

探究米诺环素在体外对常见酵母菌的药敏特点。采用Rosco纸片扩散法对168株常见的几种假丝酵母菌进行米诺环素的药敏试验。米诺环素有抑菌环的比率:白假丝酵母菌41%,光滑假丝酵母菌1.2%,热带假丝酵母菌和克柔假丝酵母菌没有抑菌环。在常见几种酵母菌中,米诺环素几乎只对白假丝酵母菌在体外有抗菌活性。     

Antifungal activity of the amyrin derivatives and in vitro inhibition of Candida albicans adhesion to human epithelial cells

AIMS: The antifungal activity of amyrin pentacyclic triterpene and 15 synthetic derivatives was evaluated against Candida species. Additionally, inhibition of adhesion of Candida albicans to human epithelial cells in vitro was determined. METHODS AND RESULTS: Esterification of alpha- and beta-amyrin with a variety of acyl chlorides produced a series of analogue derivatives. These substances were synthesized to evaluate the antifungal properties against Candida species. Among the 15 derivatives, alpha- and beta-amyrin formiate (2) and alpha- and beta-amyrin acetate (3) were the most active, inhibiting all the Candida species tested in concentrations that ranged from 30 to 250 microg ml(-1). alpha- and beta-amyrin formiate inhibited the adhesion ability of C. albicans to buccal epithelial cells (BEC) in 65.3%. CONCLUSIONS: alpha- and beta-amyrin formiate and alpha- and beta-amyrin acetate derivatives exhibited potential antifungal activity against Candida spp. and amyrin formiate showed inhibition of the adhesion ability of C. albicans to buccal epithelial cells. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated that two derivatives of amyrin pentacyclic triterpene exhibited significant antifungal activity against Candida species. Additionally, alpha- and beta-amyrin formiate was as effective as fluconazole in inhibiting the adhesion of C. albicans to buccal epithelial cells.     

PEG mediated synthesis and pharmacological evaluation of some fluoro substituted pyrazoline derivatives as antiinflammatory and analgesic agents

A new series of fluoro substituted pyrazoline derivatives 5a–g and 6a–g were synthesized in good to excellent yield from the corresponding pyrazole chalcones, 4a–g, by using polyethylene glycol-400 (PEG-400) as an alternative reaction medium. The newly synthesized compounds were characterized and screened for their in vivo antiinflammatory and analgesic activity. Compounds 5g and 6g were found to be more potent than standard drug Diclofenac and six other compounds 5b, 5c, 5f, 6b, 6c and 6f showed significant antiinflammatory activity as compared to standard drug. Compounds 5c, 5d, 5e, 5f, 6c, 6d, 6e and 6f showed significant analgesic activity as compared to standard drug Aspirin.     

Screening and evaluation of antioxidant activity of some amido-carbonyl oxime derivatives and their radical scavenging activities

The antioxidant activity of some amido-carbonyl oximes containing a C=O and –NH–R adjacent to the oxime group, [Phenyl-C(=O)-C(=N-OH)-N(-H)-Phenyl(-R)] where R= H, 4-chloro, 4-methyl, 4-methoxy, 3,4-dichloro, 3,4-dimethyl, 3-chloro-4-dimethyl, 3-chloro-4-methoxy, naphthyl and an amido-carbonyl dioxime were investigated in vitro by ferric thiocyanate, total reducing power by potassium ferricyanide reduction, 1,1-diphenyl-2- picryl-hydrazyl (DPPH^·) free radical scavenging, ferrous ions chelating, superoxide anion radical scavenging and hydrogen peroxide scavenging activity assays. The results indicated that the amido-carbonyl oximes have powerful antioxidant capacity.     

Synthesis and characterization of some hydroxypyridone derivatives and their evaluation as antimicrobial agents

The synthesis, in vitro antimicrobial activities of some novel hydroxy pyridines supported with various pharmacophores is described. Twenty-six out of the tested 58 compounds exhibited variable inhibitory effects on the growth of the tested Gram positive and Gram negative bacteria. The tested compounds revealed better activity against the Gram positive rather than the Gram negative strains. The synthesized hydroxypyridones have shown very significant inhibitory effect against Staphylococcus aureus and Bacillus subtilis. Twelve compounds namely; 5d, 5f, 6a, 6b, 8b, 18b, 18c, 19c, 21d, 22b, 22d and 23d were able to produce appreciable growth inhibitory activity against Candida albicans when compared to Clotrimazole. Among these, 22d proved to be the most potent antifungal agent.     

Antibacterial and antifungal activities of teucrium royleanum (Labiatea)

The crude methanolic extract and subsequent fractions of Teucrium royleanum (Labiatea) were screened for antibacterial and antifungal activities. Against tested pathogens, crude extract and subsequent fractions demonstrated moderate to excellent antibacterial activities. Highest antibacterial activity was displayed by the ethyl acetate fraction against S. typhi (100%), against E.coli (76.7%) and against P. aerugenosa (70.8%) followed by the chloroform fraction against S. typhi (85.7%). Similarly, the crude extract and its subsequent fractions showed mild to excellent activities in the antifungal bioassay with maximum antifungal activity against M. canis (87%) by the chloroform fraction followed by the ethyl acetate (71%) and n-butanol (70%) fractions.     

Study of antifungal activities of seven essential oils from some Iranian medicinal plants against various postharvest phytopathogenic fungi

The aim of this study was to find the antifungal activities of seven essential oils from some Iranian medicinal plants that have maximum (100%) inhibition effect on the mycelium growth of postharvest phytopathogenic fungi. Among 20 examined species belonging to three families, only 7 species could stop the mycelium growth of phytopathogenic fungi. The selected plants include Trachyspermum ammi, Zataria multiflora Boiss., Satureia hortensis, Caryophillum aromaticus, Menthe piperita, Cuminum cyminum L. and Carum carvi, and fungi include Aspergillus flavus, Botrytis cinerea, Penicillium italicum, Penicillium expansum, Penicillium commune, Rhizopus stolonifer and Rhizopus lyococcus. The results showed that the essential oil of these plants could stop the mycelium growth at 500 ppm, but could not completely inhibit the spore germination, however reduced the spore germination to 80–90%. Among the fungi Rhizopus stolonifer and Rhizopus lyococcus are more resistant to the inhibition effects of essential oils. Among the plants, Cuminum cyminum L. and Carum carvi were slightly weaker than other plants. Also except for Cuminum cyminum L. and Carum carvi, the essential oils of other plants had fungicide effect while these two plants in most cases had fugistatic effect. The results showed that these essential oils can be used as an effective alternative control method.     

Synthesis of novel tetrazole derivatives and evaluation of their antifungal activity

With the appearance of the antifungal resistance, novel antifungal agents need to be identified. In this context new 2,5-disubstituted tetrazole derivatives containing benzothiazole, benzoxazole or phenylsulfonyl moiety were synthesized by N-alkylation of aryltetrazole with 2-[(3-chloropropyl)sulfanyl]-1,3-benzothiazole or 2-[(3-chloropropyl)sulfanyl]-1,3-benzoxazole and Michael-type addition of aryltetrazole to phenyl vinyl sulfone. The chemical structures of the synthesized compounds were confirmed by means of ¹H NMR, ¹³C NMR, IR and HRMS spectral data. The compounds were tested against the moulds: Fusarium sambucinum, Fusarium oxysporum, Colletotrichum coccodes, Aspergillus niger, and the yeast Candida albicans. The results showed that among the moulds only C. coccodes was significantly sensitive to all the structures examined. All the tetrazole derivatives acted at the same level against C. albicans and demonstrated a high cell growth inhibition (97–99%) at the concentrations ranging from 16 to 0.0313 μg/mL. The mode of action of 2-({3-[5-(4-chlorophenyl)-2H-tetrazol-2-yl]propyl}sulfanyl)-1,3-benzoxazole (5c) and 2-({3-[5-(2-chlorophenyl)-2H-tetrazol-2-yl]propyl}sulfanyl)-1,3-benzoxazole (5d) was established by verifying fungal growth in the presence of osmotic protector-sorbitol. The effect of compound 5c or 5d combined with Fluconazole was determined using the checkerboard method. The calculated fractional inhibitory concentration index (FIC) indicated antagonism (FIC >1). Additionally, survival experiments with lepidopteran Galleria mellonella treated with compounds 5c and 5d were performed and demonstrated the lack of toxicity of these compounds.     

Synthesis of some imidazolyl-thioacetyl-pyrazolinone derivatives and their antinociceptive and anticancer activities

In this study, some 4-(1,5-diarylimidazol-2-yl)thioacetyl-1-phenyl-2,3-dimethyl-3-pyrazoline-5-one derivatives were prepared by reacting 4-(2-chloroacetyl)-1-phenyl-2,3-dimethyl-3-pyrazoline-5-one and 2-mercapto-1, 5-diarylimidazole derivatives. The antinociceptive and anticancer activities of the compounds obtained were investigated. It was observed that some of the compounds, 2a, 2d, 2g, and 2j, showed remarkable antinociceptive activity, and one of the compounds, 2i, showed weak anticancer activity.     

Antifungal activity of essential oils of Croton species from the Brazilian Caatinga biome

Aims: To find new antifungal agents among essential oils from Brazilian Croton species. Methods and Results: Plant leaves were steam distilled and the obtained essential oils were analyzed by gas chromatography/mass spectroscopy. The main constituents were estragole and anethole for Croton zehntneri, methyl-eugenol and bicyclogermacrene for Croton nepetaefolius and spathulenol and bicyclogermacrene for Croton argyrophylloides. The antifungal activity of essential oils was evaluated against Candida albicans, Candida tropicalis and Microsporum canis by the agar-well diffusion method and the minimum inhibitory concentration (MIC) by the broth microdilution method. Essential oils of Croton species demonstrated better activity against M. canis. Among the three plants C. argyrophylloides showed the best results, with MIC ranging from 9 to 19 μg ml⁻¹. The acute administration of the essential oil up to 3 g kg⁻¹ by the oral route to mice was devoid of overt toxicity. Conclusions: The studied essential oils are active in vitro against the dermatophyte M. canis and present relative lack of acute toxicity in vivo. Significance and Impact of the Study: Because of its antifungal activity and low toxicity, the essential oils of studied Croton species are promising sources for new phytotherapeutic agents to treat dermatophytosis.     

Ciclopirox olamine: an antifungal alternative against cryptococcosis

Aims: The in vitro activity of ciclopirox olamine was evaluated against Cryptococcus spp. obtained from the cerebrospinal fluid (CSF) of immunocompromised patients. Methods and Results: The antifungal activity of ciclopirox olamine was tested against Cryptococcus spp. obtained from the CSF of immunocompromised patients, using amphotericin B and fluconazole as controls. The minimal inhibitory concentration was determined following the microdilution method indicated by the Clinical and Laboratory Standards Institute. The minimal fungicide concentration was determined by the absence of growth on Sabouraud dextrose agar. The data obtained showed that antifungal activity of ciclopirox olamine ranged from 0·25 to 1 μg ml^?1. Conclusions: This paper underscores the importance of the antifungal potential of ciclopirox olamine against Cryptococcus spp. as an alternative treatment against systemic cryptococosis. In vivo experiments are essential for future medical use. Significance and Impact of the Study: This was the first time that ciclopirox olamine was tested against Cryptococcus spp. using the reference method. The antifungal activity of this drug against this species suggests an applicable potential for systemic cryptococcosis therapy.     

Evaluation of the Antioxidant and Antifungal Actions of the Optimized Crude Extract and Fractions from the Aerial Parts of Acanthospermum hispidum

This study investigated the phytochemical characteristics of the aerial parts of Acanthospermum hispidum, by chromatographic and spectrophotometric methods, and evaluated the antioxidant and antifungal activities of the crude extract and polyphenol-enriched fractions of the species. The phytochemical prospection showed the presence of polyphenols from the groups of hydroxycinnamic derivatives and flavonoids in the crude extract (CE) and fractions of the aerial parts of A. hispidum. In the chromatographic analysis, it was possible to observe that the fractionation process of the CE with hexane and ethyl acetate was efficient in enriching the fractions in phenolic compounds. This enrichment provided an increase in antioxidant activity by the DPPH and ABTS methods, in which it was observed a higher antioxidant activity for EAF in the DPPH test and higher activity against the ABTS radical by the fractions AqF and RAqF. The extract and fractions were effective against Candida non-Candida albicans strains, mainly against C. glabrata, C. parapsilosis and C. krusei, acting predominantly fungicidal. The results indicate that the aerial parts of A. hispidum can serve as a basis for the development of new antioxidant and antifungal products. Moreover, the fractionation process can contribute to increasing the biological potential of the species.     

Synthesis of 1-acetyl-3-(2-thienyl)-5-aryl-2-pyrazoline derivatives and evaluation of their anticancer activity

In the present study, 1-acetyl-3-(2-thienyl)-5-aryl-2-pyrazoline derivatives (1–6) were synthesized via the ring closure reaction of 1-(2-thienyl)-3-aryl-2-propen-1-ones with hydrazine hydrate in acetic acid. The chemical structures of the compounds were elucidated by IR, ¹H-NMR, ¹³C-NMR and mass spectral data and elemental analyses. MTT assay, analysis of DNA synthesis and caspase-3 activation assay were carried out to determine anticancer effects of the compounds on A549 and C6 cancer cell lines. They exhibited dose-dependent anticancer activity against A549 and C6 cancer cell lines. Anticancer activity screening results revealed that compounds 1, 2 and 4 were the most potent derivatives among these compounds. But anticancer effects of these compounds may result from different death mechanisms in A549 and C6 cell lines.     

Antifungal activity of soybean and chickpea isoflavones and their reduced derivatives

The fungicidal activity of the isoflavones from soybean (Glycine max) and chickpea (Cicer arietinum) has been studied on three food and forage contaminating fungi, Aspergillus ochraceus, Penicillium digitatum and Fusarium culmorum. The reduced derivatives of the corresponding isoflavones—the isoflavanones and the isoflavans—were also included in the investigation. For the first time in a comparative study it is shown that isoflavones and isoflavanones are variable in their activity whereas the isoflavans are moderately active inhibitors of fungal growth.     

Development of selective and reversible pyrazoline based MAO-B inhibitors: virtual screening, synthesis and biological evaluation

In an effort to develop selective MAO (monoamine oxidase) B inhibitors, structure based virtual screening was initiated on an in-house library. Top 10 HITS were synthesized and evaluated for MAO (A and B) inhibitory activity, both against human and rat enzymes. All the compounds were found selective, reversible and active in nM range (100 times more potent than selegeline) towards MAO-B. Outstanding co-relation between predicted and experimental K_i values were observed.