Antibacterial activity of constituents from Salvia buchananii Hedge (Lamiaceae)

The dichloromethane extract obtained from the aerial parts of Salvia buchananii Hedge was investigated for its antimicrobial properties following a bioassay-oriented fractionation approach. The extract displayed a clear inhibitory activity against several Gram-positive multidrug-resistant clinical strains including Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus agalactiae, Enterococcus faecium and Enterococcus faecalis. No activity was observed on Gram-negative strains and on Candida species. Phytochemical investigation of this extract led to the isolation of three new clerodane diterpenes (5, 6 and 8) and eight known clerodane diterpenes (1-4, 7, 9-11) as well as ursolic (UA) and oleanolic (OA) acids. Their structures were established by extensive 1D, 2D NMR and HR-MS spectroscopic methods. The mixture UA/OA manifested a broad and powerful activity on several Gram-positive species, while diterpenes 3, 6, 8 and 9 showed moderate inhibitory activity on the Enterococcus species.     

Cell penetrating peptide TAT can kill cancer cells via membrane disruption after attachment of camptothecin

Attachment of traditional anticancer drugs to cell penetrating peptides is an effective strategy to improve their application in cancer treatment. In this study, we designed and synthesized the conjugates TAT-CPT and TAT-2CPT by attaching camptothecin (CPT) to the N-terminus of the cell penetrating peptide TAT. Interestingly, we found that TAT-CPT and especially TAT-2CPT could kill cancer cells via membrane disruption, which is similar to antimicrobial peptides. This might be because that CPT could perform as a hydrophobic residue to increase the extent of membrane insertion of TAT and the stability of the pores. In addition, TAT-CPT and TAT-2CPT could also kill cancer cells by the released CPT after they entered cells. Taken together, attachment of CPT could turn cell penetrating peptide TAT into an antimicrobial peptide with a dual mechanism of anticancer action, which presents a new strategy to develop anticancer peptides based on cell penetrating peptides.     

Confronting the challenges of discovery of novel antibacterial agents

Bacterial resistance is inevitable and is a growing concern. It can be addressed only by discovery and development of new agents. However the discovery and development of new antibacterial agents are at an all time low. This article broadly examines the historical as well as current status of antibacterial discovery and provides some perspective as how to address some of the challenges.     

Evaluation of parent and nano-encapsulated terbium(III) complex toward its photoluminescence properties,FS-DNA,BSA binding affinity,and biological applications

BackgroundThere is a crucial need for finding and developing new compounds as the anticancer and antimicrobial agents with better activity, specific target, and less toxic side effects.ObjectivesBase on the potential anticancer properties of lanthanide complexes, in the paper, the biological applications of terbium (Tb) complex, containing 2,9-dimethyl- 1,10-phenanthroline (Me₂Phen) such as anticancer, antimicrobial, DNA cleavage ability, the interaction with FS-DNA (Fish-Salmon DNA) and BSA (Bovine Serum Albumin) was examined.MethodsThe interaction of Tb-complex with BSA and DNA was studied by emission spectroscopy, absorption titration, viscosity measurement, CD spectroscopy, competitive experiments, and docking calculation. Also, the ability of this complex to cleave DNA was reported by gel electrophoresis. Tb-complex was concurrently screened for its antibacterial activities by different methods. Besides, the nanocarriers of Tb-complex (lipid nanoencapsulation (LNEP) and the starch nanoencapsulation (SNEP)), as active anticancer candidates, were prepared. MTT technique was applied to measure the antitumor properties of these compounds on human cancer cell lines.ResultsThe experimental and docking results suggest significant binding between DNA as well as BSA with terbium-complex. Besides, groove binding plays the main role in the binding of this compound with DNA and BSA. The competitive experiment with hemin demonstrated that the terbium complex was bound at site III of BSA, which was confirmed by the docking study. Also, Tb-complex was concurrently screened for its DNA cleavage, antimicrobial, and anticancer activities. The anticancer properties of LNEP and SNEP are more than the terbium compound.ConclusionsTb-complex can bond to DNA/BSA with high binding affinity. Base on biological applications of Tb-complex, it can be concluded that this complex and its nanocarriers can suggest as novel anticancer, antimicrobial candidates.     

Metformin promotes Mycobacterium tuberculosis killing and increases the production of human β-defensins in lung epithelial cells and macrophages

Diabetes has been associated with an increased risk of developing tuberculosis. The reasons related to the increased susceptibility to develop TB in type 2 diabetes mellitus (T2DM) individuals, has not been completely elucidated. However, this susceptibility has been attributed to several factors including failures and misfunctioning of the immune system. In the present study, we aimed to determine the role of anti-hyperglycemic drugs such as glyburide, insulin, and metformin to promote the killing of mycobacteria through the regulation of innate immune molecules such as host defense peptides (HDP) in lung epithelial cells and macrophages. Our results showed that metformin reduces bacillary loads in macrophages and lung epithelial cells which correlates with higher production of β-defensin-2, -3 and -4. Since β-defensins are crucial molecules for controlling Mycobacterium tuberculosis growth, the present results suggest that the use of metformin would be the first choice in the treatment for T2DM2, in patients within tuberculosis-endemic areas.     

Synthesis and evaluation of bioactive naphthoquinones from the Brazilian medicinal plant, Tabebuia avellanedae

A series of naphthoquinones based on the naphtho[2,3-b]furan-4,9-dione skeleton such as (−)-5-hydroxy-2-(1′-hydoxyethyl)naphtho[2,3-b]furan-4,9-dione (1) and its positional isomer, (−)-8-hydroxy-2-(1′-hydoxyethyl)naphtho[2,3-b]furan-4,9-dione (2), which are secondary metabolites found in the inner bark of Tabebuia avellanedae, were stereoselectively synthesized and their biological activities were evaluated in conjunction with those of their corresponding enantiomers. Compound 1 exhibited potent antiproliferative effect against several human tumor cell lines, but its effect against some human normal cell lines was much lower than that of mitomycin. On the other hand, its enantiomer (R)-1 was less active toward the above tumor cell lines than 1. The antiproliferative effect of 2 against all tumor cell lines was significantly reduced. These results indicated the presence of the phenolic hydroxy group at C-5 is of great important for increasing antiproliferative effect. In addition, 1 also showed higher cancer chemopreventive activity than 2, while there were no significant differences between 1 and 2 in antimicrobial activity. Both compounds displayed modest antifungal and antibacterial activity (Gram-positive bacteria), whereas they were inactive against Gram-negative bacteria.     

Antimicrobial characteristics and biocompatibility of the surgical sutures coated with biosynthesized silver nanoparticles

Surgical sutures play important role during the wound healing of the surgical sites which are known to be sensitive to microbial infections. Silver nanoparticles (AgNPs) have been recently used as promising agents against multiple-drug resistant microorganisms. This study was designed to coat the sutures with silver nanoparticles obtained via a green synthesis approach. Microbial-mediated biological synthesis of AgNPs were carried out ecofriendly using Streptomyces sp. AU2 cell-free extract and deposited on silk sutures through an in situ process. Sutures coated with biosyntehsized AgNP (bio-AgNP coated sutures) were characterized using Scanning Electron Microscopy (SEM) and elemantal analysis were carried out using Energy Dispersive X-ray Spectroscopy (EDS). The silver amount released by the bio-AgNP coated sutures was calculated by Inductively Coupled Plasma-Mass Spectroscopy (ICP-MS) throughout a degradation process. Antimicrobial potential of the bio-AgNP coated sutures was determined against common pathogenic microorganisms Candida albicans, Escherichia coli and Staphylococcus aureus. To determine the biocompatibility/cytotoxicty of the bio-AgNP coated sutures, the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) assay was used through an indirect test method; that the elutions obtained by the extraction of the sutures at 1, 4, 8 and 10. days and were placed in contact with 3T3 fibroblast cell culture. To best of our knowledge, this is the first report about coating of the nonabsorbable silk sutures with silver nanoparticles biosynthesized using a microbial extract.     

New carboxamides bearing benzenesulphonamides: Synthesis,molecular docking and pharmacological properties

Ten new derivatives of benzenesulphonamide bearing carboxamide functionality were synthesized and investigated for their in vitro antimicrobial, antioxidant and in vivo anti-inflammatory activities. Compound 9d inhibited carrageenan induced rat-paw oedema at 93.81, 88.79 and 86.09% at 1 h, 2 h and 3 h administration respectively. In the antimicrobial activity, compound 9a (6.54, 6.69 and 6.64 mg/mL) was most potent against S. aureus, B. subtilis and C. albicans respectively, compound 9e (6.45 and 6.46 mg/mL) was most active against P. aeruginosa and A. niger respectively while compound 9i (6.24 mg/mL) was most active against E. coli. Only compound 9a (IC₅₀ 0.3052 mg/mL) had comparable activity with Vitamin C (IC₅₀ 0.2090 mg/mL) in the antioxidant assay.     

Synthesis of compounds having antimicrobial activity from alginate

Compounds having antimicrobial activity were synthesized from sodium alginate, the main constituent of brown algae. Sodium alginate was oxidized with sodium periodate to get alginate dialdehyde (ADA). FTIR spectrum of the ADA gave very small peak characteristic for aldehyde groups at 1720 cm⁻¹, indicating that the aldehyde group is masked somehow. It may be hydrated, involving at hemiacetal formation or hemialdol, similar to cellulose dialdehyde. Two methods were used for the condensation of ADA with o-phenylenediamine analogs to obtain the final products. The first method was stirring at room temperature and the second method was heating in microwave. The microwave method gave higher yield and shorter reaction time than the other method. The condensation reaction is considered as a shiff-base formation and the proposed mechanism was suggested. The condensation products were characterized by FTIR and UV spectra. The antimicrobial potency for five of these products in addition to the used alginate and to the precursor amines was evaluated against four pathogenic fungi and six pathogenic bacteria species.     

The membrane destabilising action of the antibacterial agent chlorhexidine

Abstract The antibacterial agent chlorhexidine has long been used as an agent for medical antisepsis. This compound is a membrane active agent which probably has its major antibacterial action by interference with the function of cellular membranes. The results demonstrated an inhibition of oxygen utilisation by bacteria which was related to falls in cellular ATP levels. There was an effect on the outer membranes of Gram-negative bacteria which allowed the release of periplasmic enzymes. The inner membrane was not ruptured but its functionality was breached and there was an inhibition of active uptake of small molecules which did not appear to be related to cellular ATP levels.