Discovery of two bombinin peptides with antimicrobial and anticancer activities from the skin secretion of Oriental fire‐bellied toad,Bombina orientalis

Amphibian skin secretions are known to contain numerous peptides with a large array of biological activities. Bombinins are a group of amphibian‐derived peptides with broad spectrum antimicrobial activities that have been only identified from the ancient toad species, Bombina. In this study, we described the identification and characterization of a novel bombinin precursor which encoded a bombinin‐like peptide (BLP‐7) and a novel bombinin H‐type peptide (named as Bombinin H‐BO) from the skin secretion of Oriental fire‐bellied toad, Bombina orientalis. The primary structures of both mature peptides were determined by combinations of molecular cloning of peptide precursor‐encoding cDNAs and mass spectrometry techniques. Secondary structure prediction revealed that both peptides had cationic amphipathic α‐helical structural features. The synthetic replicate of BLP‐7 displayed more potent antimicrobial activity than Bombinin H‐BO against Gram‐positive and Gram‐negative bacteria and yeast. Also, in vitro antitumour assay showed that both peptides possessed obvious antiproliferative activity on three human hepatoma cells (Hep G2/SK‐HEP‐1/Huh7) at the non‐toxic doses. These results indicate the peptide family of bombinins could be a potential source of drug candidates for anti‐infection and anticancer therapy.     

Isolation of peptides of the brevinin‐1 family with potent candidacidal activity from the skin secretions of the frog Rana boylii

Abstract: The emergence of strains of the human pathogen Candida albicans with resistance to commonly used antibiotics has necessitated a search for new types of antifungal agents. Six peptides with antimicrobial activity were isolated from norepinephrine‐stimulated skin secretions from the foothill yellow‐legged frog Rana boylii. Brevinin‐1BYa (FLPILASLAA¹⁰KFGPKLF CLV²⁰TKKC) was particularly potent against C. albicans [minimal inhibitory concentration (MIC) = 3 μm ] and also active against Escherichia coli (MIC = 17 μm ) and Staphylococcus aureus (MIC = 2 μm ), but its therapeutic potential for systemic use is limited by its strong hemolytic activity (HC₅₀ = 4 μm ). The single amino acid substitution (Phe¹² → Leu) in brevinin‐1BYb resulted in a fourfold lower potency against C. albicans and the additional amino acid substitutions (Lys¹¹ → Thr, Phe¹⁷ → Leu and Val²⁰ → Ile) in brevinin‐1BYc resulted in a ninefold decrease in activity. Two members of the ranatuerin‐2 family and one member of the temporin family were also isolated from the secretions but showed relatively low potency against the three microorganisms tested.     

Design,synthesis, and biological evaluation of chrysin derivatives as potential FabH inhibitors

New series of chrysin derivatives ( 4a – 4t ) were designed and synthesized by introducing different substituted piperazines at C‐7 position. Their inhibitory effects on FabH were evaluated using two Gram‐negative bacterial strains, Escherichia coli and Pseudomonas aeruginosa, and two Gram‐positive bacterial strains, Bacillus subtilis and Staphylococcus aureus. To our delight, most of these compounds exhibited a dramatic increase in inhibitory potency, compared with the control positive drugs. Among them, compound 4s exhibited the most potent inhibitory activity with IC₅₀ values of 5.78 ± 0.24 μm inhibiting E. coli FabH and potent antibacterial activity against S. aureus and E. coli with MIC of 1.25 ± 0.01, 1.15 ± 0.12 μg/mL, respectively, comparing to the control positive drugs penicillin G (7.56 ± 0.30 μm ). Docking simulation was performed to position compound 4s into the FabH active site, and the result showed that compound 4s could bind well with the FabH as potent FabH inhibitor.     

Antimicrobial peptides from the skin of the Japanese mountain brown frog,Rana ornativentris

Abstract: Six peptides with antimicrobial activity were isolated from an extract of freeze‐dried skin of the Japanese mountain brown frog Rana ornativentris. Two structurally related peptides (brevinin‐20a GLFNVFKGALKTAGKHVAGSLLNQLKCKVSGGC, 11 nmol/g dried tissue, and brevinin‐20b GIFNVFKGALKTAGKHVAGSLLNQLKCKVSGEC, 170 nmol/g) belong to the brevinin‐2 family, previously identified in Asian and European, but not North American, Ranid frogs. Four peptides (temporin‐1Oa FLPLLASLFSRLL.NH₂, 13 nmol/g; temporin‐1Ob FLPLIGKILGTI L.NH₂, 350 nmol/g; temporin‐1Oc FLPLLASLFSRLF.NH₂, 14 nmol/g; and temporin‐1Od FLPLLASLFSGLF.NH₂, 8 nmol/g) are members of the temporin family first identified in the European common frog Rana temporaria but also found in the skins of North American Ranids. The brevinin‐2 peptides showed broad‐spectrum activity against the gram‐positive bacterium, Staphylococcus aureus, the gram‐negative bacterium, Escherichia coli and the yeast Candida albicans, whereas the temporins showed potent activity only against S. aureus. The brevinins and temporins belong to the class of cationic antimicrobial peptides that adopt an amphipathic α‐helical conformation but it is significant that temporin‐1Od, which lacks a basic amino acid residue, is still active against S. aureus (minimum inhibitory concentration=13 µm compared with 2 µm for temporin‐1Oa). This suggests that strong electrostatic interaction between the peptide and the negatively charged phospholipids of the cell membrane is not an absolute prerequisite for antimicrobial activity.     

Synthesis and anti‐Candida activity of novel benzothiepino[3,2‐c]pyridine derivatives

A novel series of thiepine derivatives were synthesized and evaluated as potential antimicrobials. All the synthesized compounds were evaluated for their antimicrobial activities in vitro against the fungi Candida albicans (ATCC 10231), C. parapsilosis (clinical isolate), Gram‐negative bacterium Pseudomonas aeruginosa (ATCC 44752), and Gram‐positive bacterium Staphylococcus aureus (ATCC 25923). Synthesized compounds showed higher antifungal activity than antibacterial activity, indicating that they could be used as selective antimicrobials. Selected thiepines efficiently inhibited Candida hyphae formation, a trait necessary for their pathogenicity. Thiepine 8‐phenyl[1]benzothiepino[3,2‐c]pyridine ( 16 ) efficiently killed Candida albicans at 15.6 μg/mL and showed no embryotoxicity at 75 μg/mL. Derivative 8‐[4‐(4,5‐dihydro‐1H‐imidazol‐2‐yl)phenyl][1]benzothiepino[3,2‐c]pyridine ( 23 ) caused significant hemolysis and in vitro DNA interaction. The position of the phenyl ring was essential for the antifungal activity, while the electronic effects of the substituents did not significantly influence activity. Results obtained from in vivo embryotoxicity on zebrafish (Danio rerio) encourage further structure optimizations.     

Design,synthesis, and structure–activity relationship studies of novel pleuromutilin derivatives having a piperazine ring

A series of novel pleuromutilin derivatives possessing piperazine moieties were synthesized under mild conditions. The in vitro antibacterial activities of these derivatives against Staphylococcus aureus and Escherichia coli were tested by the agar dilution method. Structure–activity relationship studies resulted in compounds 11b , 13b , and 14a with the most potent in vitro antibacterial activity among the series (minimal inhibitory concentration = 0.0625–0.125 μg/mL). The binding of compounds 11b , 13b , and 14a to the E. coli ribosome was investigated by molecular modeling, and it was found that there is a reasonable correlation between the binding free energy and the antibacterial activity.     

Synthesis and Antimicrobial Activity of the Hybrid Molecules between Sulfonamides and Active Antimicrobial Pleuromutilin Derivative

A series of novel hybrid molecules between sulfonamides and active antimicrobial 14‐o‐(3‐carboxy‐phenylsulfide)‐mutilin were synthesized, and their in vitro antibacterial activities were evaluated by the broth microdilution. Results indicated that these compounds displayed potent antimicrobial activities in vitro against various drug‐susceptible and drug‐resistant Gram‐positive bacteria such as Staphylococci and streptococci, including methicillin‐resistant Staphylococcus aureus, and mycoplasma. In particular, sulfapyridine analog ( 6c ) exhibited more potent inhibitory activity against Gram‐positive bacteria and mycoplasma, including Staphylococcus aureus (MIC = 0.016–0.063 μg/mL), methicillin‐resistant Staphylococcus aureus (MIC = 0.016 μg/mL), Streptococcus pneumoniae (MIC = 0.032–0.063 μg/mL), Mycoplasma gallisepticum (MIC = 0.004 μg/mL), with respect to other synthesized compounds and reference drugs sulfonamide (MIC = 8–128 μg/mL) and valnemulin (MIC = 0.004–0.5 μg/mL). Furthermore, comparison between MIC values of pleuromutilin‐sulfonamide hybrids 6a–f with pleuromutilin parent compound 3 revealed that these modifications at 14 position side chain of the pleuromutilin with benzene sulfonamide could greatly improve the antibacterial activity especially against Gram‐positives.     

4‐Substituted thieno[2,3‐d]pyrimidines as potent antibacterial agents: Rational design,microwave‐assisted synthesis,biological evaluation and molecular docking studies

In an attempt to discover a new class of antibacterial agents with improved efficacy and to overcome the drug‐resistant problems, some novel 4‐substituted thieno[2,3‐d]pyrimidines have been synthesized via microwave‐assisted methodology and evaluated for their in vitro antibacterial activity against various pathogenic bacterial strains. Compounds 12 b and 13 c showed the promising inhibitory potencies against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli with MICs ranging from 2 to 10 μg/ml. Compound 13 c was also found to be highly potent against methicillin‐resistant S. aureus (MRSA) with MIC value of 4 μg/ml. Docking simulation studies have been performed to unravel the mode of action and association study indicate the binding of potent compounds with DHPS enzyme. In silico ADME studies suggest the drug‐like characteristics of the potent compounds.     

Novel Glycoconjugate of 8‐Fluoro Norfloxacin Derivatives as Gentamicin‐resistant Staphylococcus aureus Inhibitors: Synthesis and Molecular Modelling Studies

Antibiotic resistance has been the subject of interest in clinical practice due to high prevalence of antibiotic‐resistant pathogenic organisms. In view of the prevalence of lesser resistance in antibiotics belonging to aminoglycoside class of compounds viz. Food and Drug Administration‐approved gentamicin for the treatment of Staphylococcus infections, which also has instances of resistance in the clinical isolates of Staphylococcus aureus, a series of novel glycoconjugates of 8‐fluoro norfloxacin analogues with high regio‐selectivity by employing copper (I)‐catalyzed 1, 3‐dipolar cycloaddition of 1‐O‐propargyl monosaccharides has been synthesized and evaluated for the antibacterial activity against gentamicin resistance Staphylococcus aureus. Among these compounds, the compound 10g showed better antibacterial activity (MIC = 3.12  μ g/ml) than gentamicin (Escherichia coli (12.5  μ g/ml), Staphylococcus aureus (6.25  μ g/ml) and Klebsiella pneumonia (6.25  μ g/ml), including gentamicin resistant (>50  μ g/ml) strain in vitro). The docking studies suggest DNA gyrase of Staphylococcus aureus as a probable target for the antibacterial action of compound 10g .     

Antibacterial and antitubercular evaluation of dihydronaphthalenone‐indole hybrid analogs

A new series of indole appended dihydronaphthalenone hybrid analogs ( 5a–t ) have been synthesized through the Lewis acid catalyzed Michael addition of indoles to the arylidene/hetero arylidene ketones. All the synthesized derivatives are well characterized through the ¹H‐NMR, ¹³C‐NMR, HRMS spectroscopic techniques, compound 5r was further confirmed through single crystal X‐ray analysis and screened for antibacterial and antitubercular activities. Among the synthesized compounds, the minimum inhibition concentration of 5l (against Escherichia coli) and 5o & 5p (against E. coli & Staphylococcus aureus) was found to be as low as 3.12 μg/ml as compared to the standard antibacterial drug ciprofloxacin 2.5 μg/ml. In antitubercular activity, compounds 5o and 5p with minimum inhibition concentration 6.25 μg/ml were found to be comparable with that of the drugs Pyrazinamide 5 μg/ml and Streptomycin 5 μg/ml. Compounds 5i , 5j , 5m , 5n , 5q , and 5r also showed promising activity against group of organisms tested.     

Antimicrobial Properties of Brevinin‐2‐Related Peptide and its Analogs: Efficacy Against Multidrug‐Resistant Acinetobacter baumannii

Brevinin‐2 related peptide (B2RP; GIWDTIKSMG¹⁰KVFAGKILQN²⁰L.NH₂), first isolated from skin secretions of the mink frog Lithobates septentrionalis, shows broad‐spectrum antimicrobial activity but its therapeutic potential is limited by moderate hemolytic activity. The peptide adopts an α‐helical conformation in a membrane‐mimetic solvent but amphipathicity is low. Increasing amphipathicity together with hydrophobicity by the substitutions Lys¹⁶→Leu and Lys¹⁶→Ala increased hemolytic activity approximately fivefold without increasing antimicrobial potency. The substitution Leu¹⁸→Lys increased both cationicity and amphipathicity but produced decreases in both antimicrobial potency and hemolytic activity. In contrast, increasing cationicity of B2RP without changing amphipathicity by the substitution Asp⁴→Lys resulted in a fourfold increase in potency against Escherichia coli [minimal inhibitory concentration (MIC) = 6 μm ) and twofold increases in potency against Staphylococcus aureus (MIC = 12.5 μm ) and Candida albicans (MIC = 6 μm ) without changing significantly hemolytic activity against human erythrocytes (LC₅₀ = 95 μm ). The emergence of antibiotic‐resistant strains of the Gram‐negative bacterium Acinetobacter baumannii constitutes a serious risk to public health. B2RP (MIC = 3–6 μm ) and [Lys⁴]B2RP (MIC = 1.5–3 μm ) potently inhibited the growth of nosocomial isolates of multidrug‐resistant Acinetobacter baumannii. Although the analogs [Lys⁴, Lys¹⁸]B2RP and [Lys⁴, Ala¹⁶, Lys¹⁸]B2RP showed reduced potency against Staphylococcus aureus, they retained activity against Acinetobacter baumannii (MIC = 3–6 μm ) and had very low hemolytic activity (LC₅₀ > 200 μm ).     

Synthesis and Antimicrobial Activities of a Novel Series of Heterocyclic α‐Aminophosphonates

Two series of novel α‐aminophosphonates having heterocyclic moieties were synthesized in high yields. The structures of the newly synthesized compounds were confirmed by their elemental analyses, IR, ¹H NMR and MS spectral data. These compounds were screened for their antibacterial activities against Escherichia coli (NCIM2065) as a Gram‐negative bacterium, Bacillus subtilis (PC1219) and Staphylococcus aureus (ATCC25292) as Gram‐positive bacteria, and Candida albicans and Saccharomyces cerevisiae as fungi. The minimum inhibitory concentrations (MICs) of the synthesized compounds show high antibacterial and antifungal activities at low concentrations (10–1000 µg/mL). Furthermore, their lethal doses indicated that such compounds are safe for use as antimicrobial agents.     

Potent antibacterial activity of dihydydropyrimidine‐1,3,5‐triazines via inhibition of DNA gyrase and antifungal activity with favourable metabolic profile

The compounds were tested against panel of three Gram‐positive, viz. Staphylococcus aureus, Bacillus subtilis, Bacillus cereus and three Gram‐negative bacterial strains viz. Pseudomonas aeruginosa, Escherichia coli, and Proteus vulgaris where they showed significant to moderate antibacterial activity. The compound also showed considerable antibiofilm activity against S. aureus and B. subtilis. The most potent compounds 7l and 7m found bacteriostatic in time‐kill assay via inhibition of DNA gyrase enzyme and interacting with Glu58, Val130, Ile175 and Ile186 via numerous H‐bonds as revealed by docking. In S. aureus‐induced murine infection model, compound 7m showed dose‐dependent reduction of viability of bacteria with maximum activity in 25 mg/kg treated group. The antifungal activity against human fungal pathogens was also estimated, where these compounds showed considerable inhibitory activity as compared to standard. The metabolic liability of compound 7m was determined using RS‐Predictor and MetaPrint 2D React. The molecules were proved as effective antibacterial agent via inhibition of DNA gyrase as a mechanism together with significant antifungal activity.     

Leptoglycin: A new Glycine/Leucine-rich antimicrobial peptide isolated from the skin secretion of the South American frog Leptodactylus pentadactylus (Leptodactylidae)

Antimicrobial peptides are components of innate immunity that is the first-line defense against invading pathogens for a wide range of organisms. Here, we describe the isolation, biological characterization and amino acid sequencing of a novel neutral Glycine/Leucine-rich antimicrobial peptide from skin secretion of Leptodactylus pentadactylus named leptoglycin. The amino acid sequence of the peptide purified by RP-HPLC (C₁₈ column) was deduced by mass spectrometric de novo sequencing and confirmed by Edman degradation: GLLGGLLGPLLGGGGGGGGGLL. Leptoglycin was able to inhibit the growth of Gram-negative bacteria Pseudomonas aeruginosa, Escherichia coli and Citrobacter freundii with minimal inhibitory concentrations (MICs) of 8 μM, 50 μM, and 75 μM respectively, but it did not show antimicrobial activity against Gram-positive bacteria (Staphylococcus aureus, Micrococcus luteus and Enterococcus faecalis), yeasts (Candida albicans and Candida tropicalis) and dermatophytes fungi (Microsporum canis and Trichophyton rubrum). No hemolytic activity was observed at the 2-200 μM range concentration. The amino acid sequence of leptoglycin with high level of glycine (59.1%) and leucine (36.4%) containing an unusual central proline suggests the existence of a new class of Gly/Leu-rich antimicrobial peptides. Taken together, these results suggest that this natural antimicrobial peptide could be a tool to develop new antibiotics.     

Structure‐based Design,Synthesis, and Biological Evaluation of Isatin Derivatives as Potential Glycosyltransferase Inhibitors

Peptidoglycan glycosyltransferase (PGT) has been shown to be an important pharmacological target for the inhibition of bacterial cell wall biosynthesis. Structure‐based virtual screening of about 3 000 000 commercially available compounds against the crystal structure of the glycosyltransferase (GT) domain of the Staphylococcus aureus penicillin‐binding protein 2 (S. aureus PBP2) resulted in identification of an isatin derivative, 2‐(3‐(2‐carbamimidoylhydrazono)‐2‐oxoindolin‐1‐yl)‐N‐(m‐tolyl)acetamide ( 4 ) as a novel potential GT inhibitor. A series of 4 derivatives were synthesized. Several compounds showed more active antimicrobial activity than the initial hit compound 4 , in particular 2‐(3‐(2‐carbamimidoylhydrazono)‐2‐oxoindolin‐1‐yl)‐N‐(3‐nitrophenyl)acetamide ( 4l ), against Gram‐positive Bacillus subtilis and S. aureus with MIC values of 24 and 48 μg/mL, respectively. Saturation transfer difference (STD) NMR study revealed that there is a binding contact between 4l and the GT domain of S. aureus PBP2. Competitive STD‐NMR further proved that 4l and moenomycin A bind to GT domain in a competitive manner. Molecular docking study suggests a potential binding pocket of 4l in the GT domain of S. aureus PBP2. Taken together, compound 4l would provide a new scaffold for further development of potent GT inhibitors.     

Antimicrobial,modulatory and chemical analysis of the oil of Croton limae

Context: Croton sp. are plants with a well-reported antimicrobial activity. Croton limae A.P. Gomes, M.F. Sales P.E. Berry (Euphorbiaceae), known as ‘marmeleiro-prateado’, is commonly used to manage abdominal pain in Brazil.

Objective: This work evaluates the phytochemical composition, antimicrobial and modulatory activities of the essential oil of C. limae leaves (EOCL).

Materials and methods: The minimum inhibitory concentration (MIC) and the modulation of the antibiotic activity were determined using a microdilution method. The concentration of EOCL ranged between 512 and 8?μg/mL. Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Candida tropicalis, C. krusei and C. albicans strains were used in the MIC and modulation assays. The antibiotics, amikacin, gentamicin and neomycin, and the antifungals, amphotericin B, benzoylmetronidazole and nystatin, were used in concentrations ranging between 2500 and 2.5?μg/mL. The phytochemical analysis of the EOCL was performed through gas chromatography coupled to a mass spectrometer (GC/MS).

Results: Only Staphylococcus aureus was inhibited by a clinically relevant concentration of EOCL (MIC 512?μg/mL). Synergism between the EOCL and amikacin against S. aureus (9.76?μg/mL) and E. coli (39.062?μg/mL); neomycin against E. coli (2.44?μg/mL); and benzoylmetronidazole against C. krusei (256?μg/mL) were observed. The GC/MS analysis identified cedrol, eucalyptol and α-pinene as the main compounds of EOCL.

Conclusion: EOCL inhibited the growth of S. aureus and potentiated the antibiotic and antifungal effects of drugs against all bacterial and Candida strains, respectively.     

Design,Synthesis, Antibacterial Evaluation and Docking Study of Novel 2‐Hydroxy‐3‐(nitroimidazolyl)‐propyl‐derived Quinolone

A novel series of 2‐hydroxy‐3‐(nitroimidazolyl)‐propyl‐derived quinolones 6a – o were synthesized and evaluated for their in vitro antibacterial activity. Most of the target compounds exhibited potent activity against Gram‐positive strains. Among them, moxifloxacin analog 6n displayed the most potent activity against Gram‐positive strains including S. epidermidis (MIC = 0.06 μg/mL), MSSE (MIC = 0.125 μg/mL), MRSE (MIC = 0.03 μg/mL), S. aureus (MIC = 0.125 μg/mL), MSSA (MIC = 0.125 μg/mL), (MIC = 2 μg/mL). Its activity against MRSA was eightfold more potent than reference drug gatifloxacin. Finally, docking study of the target compound 6n revealed that the binding model of quinolone nucleus was similar to that of gatifloxacin and the 2‐hydroxy‐3‐(nitroimidazolyl)‐propyl group formed two additional hydrogen bonds.     

Preliminary studies on the antibacterial activity of crude extracts and alkaloids from species of Aspidosperma

Screening tests of hydroethanolic crude extracts of six species of Aspidosperma (Apocynaceae) against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa were performed. Aspidosperma ramiflorum Muell. Arg. showed good activity against Bacillus subtilis with MIC and MBC of 15.7 and 125?μg/mL, moderate activity against Staphylococcus aureus with MIC and MBC of 250 and 500?μg/mL, and weak activity against Escherichia coli with MIC and MBC of 1000?μg/mL. Aspidosperma pyricolum Muell. Arg. (MIC/MBC 125/250?μg/mL) and Aspidosperma olivaceum Muell. Arg. (MIC/MBC 250/?>?1000?μg/mL) displayed moderate antibacterial activity against Bacillus subtilis. Separation of the crude extract of Aspidosperma ramiflorum was performed according to the usual acid–base process, which produces alkaloid mixtures and closely related metabolites. The basic fraction was active against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli, with MICs of 31.2, 62.5, and 250?μg/mL, respectively. The basic fractions were more active than the acid fractions, probably because they contained some active alkaloids and/or closely related metabolites absent from the other fractions, or they contained a higher concentration of these active compounds.     

Design,synthesis and in vitro antiplasmodial activity of some bisquinolines against chloroquine‐resistant strain

A series of novel bisquinoline compounds comprising N¹‐(7‐chloroquinolin‐4‐yl) ethane‐1,2‐diamine and 7‐chloro‐N‐(2‐(piperazin‐1‐yl)ethyl)quinolin‐4‐amine connected with 7‐chloro‐4‐aminoquinoline containing various amino acids is described. We have bio‐evaluated the compounds against both chloroquine‐sensitive (3D7) and chloroquine‐resistant (K1) strains of Plasmodium falciparum in vitro. Among the series, compounds 4 and 7 exhibited 1.8‐ and 10.6‐fold superior activity as compared to chloroquine (CQ; IC₅₀ = 0.255 ± 0.049 μm ) against the K1 strain with IC₅₀ values 0.137 ± 0.014 and 0.026 ± 0.007 μm , respectively. Furthermore, compound 7 also displayed promising activity against the 3D7 strain (IC₅₀ = 0.024 ± 0.003 μm ) of P. falciparum when compared to CQ. All the compounds in the series displayed resistance factor between 0.57 and 4.71 as against 51 for CQ. These results suggest that bisquinolines can be explored for further development as new antimalarial agents active against chloroquine‐resistant P. falciparum.     

Synthesis and biological activities of new Mannich bases of chlorokojic acid derivatives

A novel series of 6-chloromethyl-3-hydroxy-2-substituted 4H-pyran-4-one derivatives were synthesized and tested for their antibacterial, antifungal and antiviral in vitro properties. In the view of activity results, compounds 8–11 (MIC: 8 μg/ml) were more remarkably active against Staphylococcus aureus and Enterococcus faecalis. Compounds 1–7 were highly active against Candida albicans and C. parapsilosis with MIC value of 8 μg/ml. Compound 9 bearing 3-chlorophenyl moiety was determined to be the most active compound against RNA virus PI-3.