Telepharmacy in Indonesia: Navigating Knowledge, Perception, and Readiness Among 6,000 Pharmacists and Related Sociodemographic Determinants.

Introduction: Telepharmacy can improve the delivery of pharmaceutical care services to patients. However, there are limited data regarding the knowledge, perceptions, and readiness (KPR) for telepharmacy in Indonesia. In this cross-sectional survey study, we assessed KPR and associated factors among Indonesian pharmacists, aiming to implement telepharmacy services in the future. Methods: Eligible participants were recruited from all provinces of Indonesia through a 24-item instrument. KPR scores were classified as low, moderate, and high. Sociodemographic characteristics and KPR of participants were summarized using descriptive statistics. Bivariate/multivariate ordinal logistic regression analyses were conducted to identify independent determinants of KPR. An adjusted odds ratio (AOR) with a 95% confidence interval (CI) was calculated for each determinant. Results: A total of 6,059 pharmacists provided responses. Overall, 58.28% had a high knowledge score, and 63.51% expressed moderate perceptions toward telepharmacy services. Moreover, 70.21% showed a moderate level of readiness. Gender (male; AOR: 1.21 [95% CI: 1.06-1.39]), stable internet access (AOR: 0.75 [95% CI: 0.64-0.86]), and central region (AOR: 1.13 [95% CI: 0.99-1.29]) were significantly associated with perception toward telepharmacy. Readiness was significantly associated with age (17-25 years; AOR: 0.73 [95% CI: (0.60-0.89]), gender (male; AOR: 0.83 [95% CI: 0.72-0.95]), stable internet access (AOR: 0.75 [95% CI: 0.64-0.89]), education level (master/doctoral; AOR: 1.33 [95% CI: 1.06-1.67]), and central region (AOR: 1.29 [95% CI: 1.12-1.49]). Interestingly, knowledge levels were not significantly correlated with specific factors. Conclusions: Participants demonstrated high knowledge, without significant influencing factors. However, they showed moderate perceptions and readiness levels, influenced by sociodemographic factors, including gender, age, education level, internet access, and regional disparities. Therefore, targeted interventions (e.g., telepharmacy training and regional outreach) are imperative to enhancing perceptions and readiness, fostering the effective integration of telepharmacy services, and advancing pharmaceutical care in Indonesia.

Stereoselective synthesis and antiproliferative activity of allo-gibberic acid-based 1,3-aminoalcohol regioisomers.

A new library of allo-gibberic acid-based aminoalcohol regioisomers was synthesised stereoselectively starting from commercially available gibberellic acid, which yields allo-gibberic acid under mild acidic conditions. The successful formation of hydroxymethyl ketone derivative 5, by acid-mediated rearrangement of previously prepared epoxide, paved the way to obtain the desired 1,3-aminoalcohols through Schiff base formation. To obtain the desired regioisomers, the primary alcohol functionality of 5 was subjected to mesylation, then replaced with either primary amine or sodium azide. The formed azide derivative was subjected to either CuAAC reaction to obtain 1,2,3-triazoles or underwent Pd-catalysed hydrogenolysis to obtain primary aminoalcohol, which was further transformed into 1,3-aminoalcohols by reductive alkylation. All prepared aminoalcohols were identified in a satisfactory manner using modern spectroscopic techniques and assessed for their antiproliferative activity against a panel of human cancer cell lines. The antiproliferative effects of the prepared compounds were assayed by in vitro MTT method against a panel of human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231). A significant difference was observed in the antiproliferative activity between the regioisomers. Some compounds exerted outstanding activities against the malignant cells with limited action on fibroblasts, indicating considerable cancer selectivity.

CuAAC-Based Synthesis, Copper-Catalyzed Aldehyde-Forming Hydrolytic Fission and Antiproliferative Evaluation of Novel Ferrocenoylamino-Substituted Triazole-Tethered Quinine-Chalcone Hybrids.

A series of novel triazole-tethered ferrocenoylamino-substituted cinchona-chalcone hybrids along with two representative benzoylamino-substituted reference compounds were prepared by three methods of CuAAC chemistry. In line with the limited success or complete failure of attempted conversions with low catalyst loadings, by means of DFT modeling studies, we demonstrated that a substantial part of the Cu(I) ions can be chelated and thus trapped in the aroylamino-substituted cinchona fragment and all of the accessible coordinating sites of the chalcone residues. Accordingly, increased amounts of catalysts were used to achieve acceptable yields; however, the cycloadditions with para-azidochalcones were accompanied by partial or complete aldehyde-forming hydrolytic fission of the enone C=C bond in a substituent-, solvent- and copper load-dependent manner. The experienced hydrolytic stability of the hybrids obtained by cycloadditions with ortho-azidochalcones was interpreted in terms of relative energetics, DFT reactivity indices and MO analysis of simplified models of two isomer copper-enone complexes. The novel hybrids were evaluated on HeLa, MDA-MB-231 and A2780 cell lines and showed substantial activity at low-to-submicromolar concentrations. An organometallic model carrying 3,4,5-trimethoxyphenyl residue in the enone part with a para-disubstituted benzene ring in the central skeletal region was identified as the most potent antiproliferative lead, characterized by submicromolar IC50 values measured on the three investigated cells. The biological assays also disclosed that this ferrocenoylamino-containing lead compound displays a ca. two- to five-fold more substantial antiproliferative effect than its benzoylamino-substituted counterpart.

Stereoselective Synthesis and Antiproliferative Activity of Steviol-Based Diterpene 1,3-Aminoalcohol Regioisomers.

A series of novel diterpene-type 1,3-aminoalcohols and their regioisomers have been synthesised from natural stevioside in a stereoselective manner. The key intermediate ß-keto alcohol was prepared using Wagner-Meerwein rearrangement of the epoxide derived from steviol methyl ester. The primary aminoalcohol was formed via Raney-nickel-catalysed hydrogenation of an oxime, and a versatile library of aminoalcohols was synthesised using a Schiff base with the primary amines. The aminoalcohol regioisomers were prepared from the mesylate of the ß-keto alcohols. The corresponding primary aminoalcohol was formed via the palladium-catalysed hydrogenation of hydroxyl-azide, and click reactions of the latter were also carried out. The new compounds were characterised using 1D- and 2D-NMR techniques and HRMS measurements. The in vitro investigations showed high inhibition of cell growth in human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231) in the case of naphthalic N-substituted derivatives. The antiproliferative effects were assayed using the MTT method.

Repositioning of HMG-CoA Reductase Inhibitors as Adjuvants in the Modulation of Efflux Pump-Mediated Bacterial and Tumor Resistance.

Efflux pump (EP)-mediated multidrug resistance (MDR) seems ubiquitous in bacterial infections and neoplastic diseases. The diversity and lack of specificity of these efflux mechanisms raise a great obstacle in developing drugs that modulate efflux pumps. Since developing novel chemotherapeutic drugs requires large investments, drug repurposing offers a new approach that can provide alternatives as adjuvants in treating resistant microbial infections and progressive cancerous diseases. Hydroxy-methyl-glutaryl coenzyme-A (HMG-CoA) reductase inhibitors, also known as statins, are promising agents in this respect. Originally, statins were used in the therapy of dyslipidemia and for the prevention of cardiovascular diseases; however, extensive research has recently been performed to elucidate the functions of statins in bacterial infections and cancers. The mevalonate pathway is essential in the posttranslational modification of proteins related to vital eukaryotic cell functions. In this article, a comparative review is given about the possible role of HMG-CoA reductase inhibitors in managing diseases of bacterial and neoplastic origin. Molecular research and clinical studies have proven the justification of statins in this field. Further well-designed clinical trials are urged to clarify the significance of the contribution of statins to the lower risk of disease progression in bacterial infections and cancerous diseases.

Isolation and NMR Scaling Factors for the Structure Determination of Lobatolide H, a Flexible Sesquiterpene from Neurolaena lobata.

A new flexible germacranolide (1, lobatolide H) was isolated from the aerial parts of Neurolaena lobata. The structure elucidation was performed by classical NMR experiments and DFT NMR calculations. Altogether, 80 theoretical level combinations with existing 13C NMR scaling factors were tested, and the best performing ones were applied on 1. 1H and 13C NMR scaling factors were also developed for two combinations utilizing known exomethylene containing derivatives, and the results were complemented by homonuclear coupling constant (JHH) and TDDFT-ECD calculations to elucidate the stereochemistry of 1. Lobatolide H possessed remarkable antiproliferative activity against human cervical tumor cell lines with different HPV status (SiHa and C33A), induced cell cycle disturbance and exhibited a substantial antimigratory effect in SiHa cells.

Stereoselective Synthesis and Antiproliferative Activities of Tetrafunctional Diterpene Steviol Derivatives.

A new family of diterpene-type aminotriol derivatives has been synthesised from stevioside in a stereoselective manner. The key intermediate spiro-epoxide was prepared through the methyl ester of the allilyc diol derived from steviol. The oxirane ring was opened with primary and secondary amines, providing a versatile library of aminotriols. The corresponding primary aminotriol was formed by palladium-catalysed hydrogenation, and an N,O-heterocyclic compound was synthesised in a regioselective reaction. All new compounds were characterised by 1D- and 2D-NMR techniques and HRMS measurements. In our in vitro investigations, we found that the aromatic N-substituted derivatives exhibited high inhibition of cell growth on human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231). The antiproliferative activities were assayed by the MTT method. Furthermore, the introduction of an additional hydroxy group slightly increased the biological activity. The drug-likeness of the compounds was assessed by in silico and experimental physicochemical characterisations, completed by kinetic aqueous solubility and in vitro intestinal-specific parallel artificial membrane permeability assay (PAMPA-GI) measurements.

New 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinazoline and 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinoline Derivatives: Synthesis and Biological Evaluation as Novel Anticancer Agents by Targeting G-Quadruplex.

The syntheses of novel 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinazolines 12 and 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinolines 13 are reported here in six steps starting from various halogeno-quinazoline-2,4-(1H,3H)-diones or substituted anilines. The antiproliferative activities of the products were determined in vitro against a panel of breast (MCF-7 and MDA-MB-231), human adherent cervical (HeLa and SiHa), and ovarian (A2780) cell lines. Disubstituted 6- and 7-phenyl-bis(3-dimethylaminopropyl)aminomethylphenyl-quinazolines 12b, 12f, and 12i displayed the most interesting antiproliferative activities against six human cancer cell lines. In the series of quinoline derivatives, 6-phenyl-bis(3-dimethylaminopropyl)aminomethylphenylquinoline 13a proved to be the most active. G-quadruplexes (G4) stacked non-canonical nucleic acid structures found in specific G-rich DNA, or RNA sequences in the human genome are considered as potential targets for the development of anticancer agents. Then, as small aza-organic heterocyclic derivatives are well known to target and stabilize G4 structures, their ability to bind G4 structures have been determined through FRET melting, circular dichroism, and native mass spectrometry assays. Finally, telomerase inhibition ability has been also assessed using the MCF-7 cell line.

Stereoselective Synthesis and Application of Gibberellic Acid-Derived Aminodiols.

A series of gibberellic acid-based aminodiols was designed and synthesized from commercially available gibberellic acid. Exposure of gibberellic acid to hydrochloric acid under reflux conditions resulted in aromatization followed by rearrangement to form allo-gibberic acid. The key intermediate, ethyl allo-gibberate, was prepared according to literature methods. Epoxidation of key intermediate and subsequent ring-opening of the corresponding epoxide with different nucleophiles resulted in N-substituted aminodiols. The regioselective ring closure of N-benzyl-substituted aminodiol with formaldehyde was also investigated. All aminodiol derivatives were well characterized using modern spectroscopic techniques and evaluated for their antiproliferative activity against a panel of human cancer cell lines. In addition, structure-activity relationships were examined by assessing substituent effects on the aminodiol systems. The results indicated that aminodiols containing aromatic rings on their nitrogen substituents displayed significant cytotoxic effects. Among these agents, N-naphthylmethyl-substituted aminodiols were found to be the most potent candidates in this series. One of these molecules exhibited a modest cancer selectivity determined by non-cancerous fibroblast cells. A docking study was also made to exploit the observed results.

Antimicrobial, Multidrug Resistance Reversal and Biofilm Formation Inhibitory Effect of Origanum majorana Extracts, Essential Oil and Monoterpenes.

Origanum majorana L. is a widely used medicinal plant; its distilled oil and preparations are extensively utilised in the phytotherapy and food industries. The objective of this study is to evaluate the extracts and the essential oil (EO) of Origanum majorana L, and its monoterpenes for antimicrobial, bacterial multidrug resistance reversing, and biofilm formation inhibitory potency. The composition of EO and n-hexane extract was characterized by GC-MS. In the essential oil terpinen-4-ol (24.92%), trans-sabinene hydrate (25.18%), γ-terpinene (6.48%), cis-sabinene hydrate (5.44%), p-cymene (4.72%), sabinene (4.53%), α-terpineol (4.43%), and α-terpinene (3.00%) were found as the main constituents while trans-sabinene hydrate (1.43%), and terpinen-4-ol (0.19%) were detected in the n-hexane extract besides a series of hydrocarbons. The antibacterial activity of EO and terpinen-4-ol, α-terpinene, and linalool was also assessed against sensitive and drug-resistant S. aureus, and E. coli strains with MIC values of 0.125-0.250% and 30-61 µM, respectively. In the efflux pump (EP) inhibitory assay, made by the ethidium bromide accumulation method in E. coli ATCC 25922, and AG100 and S. aureus ATCC 25923, and MRSA ATCC 43300 strains, EO exhibited substantial activity, especially in the E. coli ATCC 25922 strain. Among the EO constituents, only sabinene was an EP inhibitor in sensitive Escherichia strain. In the case of S. aureus strains, EO and sabinene hydrate exhibited moderate potency on the drug-resistant phenotype. The antibiofilm effects of the samples were tested by crystal violet staining at sub-MIC concentration. γ-Terpinene, terpinen-4-ol, sabinene, sabinene hydrate and linalool were found to be effective inhibitors of biofilm formation (inhibition 36-86%) on E. coli ATCC 25922 and S. aureus MRSA ATCC 43300, while EO was ineffective on these strains. In contrast to this, biofilms formed by E. coli AG100 and S. aureus ATCC 25923 were significantly inhibited by the EO; however, it was not affected by any of the monoterpenes. This observation suggests that the antibiofilm effect might be altered by the synergism between the components of the essential oil.

Spray-dried indomethacin-loaded polymeric micelles for the improvement of intestinal drug release and permeability.

Current study aimed to develop a spray-dried powder containing indomethacin (IND)-loaded polymeric micelles which can be administered perorally as a dissolved powder to enhance the drug release and permeability of the active substance. The resulting low dense spray-dried spherical particles have decreased particle size (7.21 µm) in monodisperse distribution. The polymeric micelles had a nano size range (130 nm) also in monodisperse size distribution. These nanoparticulate properties and the high encapsulation efficiency (> 80%) lead to the improvement of gastrointestinal drug release in fasted and fed state conditions. Following second order and Higuchi kinetics, a rapid drug release was experienced exceeding the initial IND suspension. In vitro cell line studies on Caco-2 human colorectal adenocarcinoma cells showed that the formulation does not increase the toxicity of initial IND, therefore can be considered safe for oral application. Ex vivo semiquantitative and quantitative studies were performed on porcine small intestine where increased flux and permeability values of IND were achieved. The physical stability of the solid formulation was sufficient through a 6-month intermediate study caused by the hydrogen-bond formation between IND and the micelle-forming co-polymer.

Development of Lomustine and n-Propyl Gallate Co-Encapsulated Liposomes for Targeting Glioblastoma Multiforme via Intranasal Administration.

This work aimed to develop lomustine (LOM) and n-propyl gallate (PG)-loaded liposomes suitable for targeting glioblastoma multiforme (GBM) via the auspicious nose-to-brain drug delivery pathway. The therapeutical effect of LOM, as a nitrosourea compound, can be potentiated by PG suitable for enhanced anti-cancer therapy. Nose-to-brain delivery of PG and LOM combined in liposomes can overcome the poor water solubility, absorption properties, and toxicity issues in the systemic circulation. Optimization and characterization of the liposomal carrier with binary drug contents were carried out in order to achieve adequate encapsulation efficiency, loading capacity, drug release, and ex vivo permeation. The optimized liposome co-encapsulated with both drugs showed suitable Z-average (127 ± 6.9 nm), size distribution (polydispersity index of 0.142 ± 0.009), zeta potential (-34 ± 1.7 mV), and high encapsulation efficacy (63.57 ± 1.3% of PG and 73.45 ± 2.2% of LOM, respectively) meeting the acceptance criteria of nose-to-brain transport for both drugs. MTT assays of PG-LOM formulations were also conducted on NIH/3T3 (murine embryonic fibroblast), U87 (glioblastoma), and A2780 (ovarian cancer) cell lines indicating reduced an antiproliferative effect on all types of cells. Our results supported the use of this novel combination of LOM and PG in a liposomal formulation as a promising carrier for glioblastoma targeting via the intranasal route.

Isolation, Structure Determination of Sesquiterpenes from Neurolaena lobata and Their Antiproliferative, Cell Cycle Arrest-Inducing and Anti-Invasive Properties against Human Cervical Tumor Cells.

Seven new germacranolides (1-3, 5-8), among them a heterodimer (7), and known germacranolide (4), eudesmane (9) and isodaucane (10) sesquiterpenes were isolated from the aerial parts of Neurolaena lobata. Their structures were determined by using a combination of different spectroscopic methods, including HR-ESIMS and 1D and 2D NMR techniques supported by DFT-NMR calculations. The enantiomeric purity of the new compounds was investigated by chiral HPLC analysis, while their absolute configurations were determined by TDDFT-ECD and OR calculations. Due to the conformationally flexible macrocycles and difficulties in assigning the relative configuration, 13C and 1H NMR chemical shift and ECD and OR calculations were performed on several stereoisomers of two derivatives. The isolated compounds (1-10) were shown to have noteworthy antiproliferative activities against three human cervical tumor cell line with different HPV status (HeLa, SiHa and C33A). Additionally, lobatolide C (6) exhibited substantial antiproliferative properties, antimigratory effect, and it induced cell cycle disturbance in SiHa cells.

Investigation of natural phenanthrenes and the antiproliferative potential of juncusol in cervical cancer cell lines.

BACKGROUND: Phenanthrenes isolated from Juncus species possess different biological activities, including antiproliferative and antimigratory effects. PURPOSE: In this study, nine phenanthrenes isolated from the roots of Juncus inflexus were investigated for their antiproliferative activity on several gynecological cancer cell lines, using non-cancerous cells as controls. METHODS: Antiproliferative activities of the compounds were determined by means of MTT assay. Flow cytometry was used for cell cycle analysis and determination of mitotic cells. Activities of caspase-3, -8, and -9 were detected by colorimetric kits. Tubulin polymerization was followed by kinetic absorbance determination. Action on tumor cell migration was described using wound healing assay. Western blot assays were used to determine apoptosis-related factors at protein level. RESULTS: Among the compounds tested, juncusol exhibited the most substantial antiproliferative effect against cervical cancer HeLa cells. It was also revealed that juncusol has a distinct growth inhibitory effect in cervical cancer cell lines of various HPV status: it was highly active in HPV type 18-positive HeLa cells, while it was inactive in HPV type 16-positive SiHa and CaSki cells. Cell cycle analysis showed an increase in G2/M and subG1 cell populations after juncusol treatment. Caspase-3, -8, and -9 were detected to be activated by juncusol in HeLa cells, indicating that juncusol induces apoptotic cell death. Moreover, juncusol inhibited tubulin polymerization, as well as EGFR activation, suggesting two possible additional mechanisms that may account for juncusol's inducing a G2/M-phase cell cycle arrest and inhibiting cell migration. CONCLUSION: These results suggest that juncusol is a potent antiproliferative agent against HPV-18 related cervical cancer and may be considered as a lead compound for the development of innovative anticancer agents.

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence.

Multistep syntheses of novel 17ß-pyrazol-5'-ones in the Δ5-androstane series were efficiently carried out from pregnenolone acetate. A steroidal 17-carboxylic acid was first synthesized as a norpregnene precursor by the bromoform reaction and subsequent acetylation. Its CDI-activated acylimidazole derivative was then converted to a ß-ketoester containing a two carbon atom-elongated side chain than that of the starting material. A Knorr cyclization of the bifunctional 1,3-dicarbonyl compound with hydrazine and its monosubstituted derivatives in AcOH under microwave heating conditions led to the regioselective formation of 17-exo-heterocycles in good to excellent yields. The suppression of an acid-catalyzed thermal decarboxylation of the ß-ketoester and thus a significant improvement in the yield of the desired heterocyclic products could be achieved by the preliminary liberation of the arylhydrazines from their hydrochloride salts in EtOH in the presence of NaOAc. The reaction rates were found to depend on the electronic character of the substituent present in the phenylhydrazine applied. The antiproliferative activities of the structurally related steroidal pyrazol-5'-ones and their deacetylated analogs were screened on three human adherent breast cancer cell lines (MCF7, T47D and MDA-MB-231): the microculture tetrazolium assay revealed that some of the presented derivatives exerted cell growth inhibitory effects on some of these cell lines comparable to those of the reference compound, cisplatin.

Antiproliferative Effects of Various Furanoacridones Isolated from Ruta graveolens on Human Breast Cancer Cell Lines.

BACKGROUND/AIM: Thanks to its biologically active constituents, Ruta graveolens L. (Rutaceae) is a widely used medicinal plant. In our study, six furanoacridone alkaloids isolated from Ruta graveolens were investigated for their antiproliferative and pro-apoptotic effects on human breast cancer cell lines (MCF-7, MDA-MB-361, MDA-MB-231 and T47D). MATERIALS AND METHODS: The cell lines were pretreated with alkaloid components (rutacridone, isogravacridone chlorine (IGC), gravacridonediol monomethyl ether, gravacridonediol, gravacridonetriol, a 1:1 mixture of gravacridonetriol and - diol monoglucosides) and their antiproliferative effects were determined by the MTT assay. RESULTS: IGC had the most marked effect on cell proliferation of MDA-MB-231 (half maximal inhibitory concentration (IC50)=2.27 µM). Cell-cycle analysis was applied to quantify the effect of IGC on subpopulations of MDA-MB-231 and MCF-7 cells. It caused a cell-cycle disturbance by decreasing the G2/M and G0/G1 and increasing the S phase and the appearance of the subdiploid (sub-G1) population. Hoechst 33258-propidium iodide staining was used to evaluate the morphological changes in IGC-pretreated MDA-MB-231 and MCF-7 cells, revealing the appearance of apoptotic features. IGC was found to cause a modest activation of caspase-3 and -9, but not caspase-8, indicating the activation of an intrinsic apoptotic pathway in MDA-MB-231 cells. CONCLUSIONS: These in vitro findings indicate that furanoacridones are suitable candidates for anticancer drug development.

Synthesis of novel 17-(4'-formyl)pyrazolylandrosta-5,16-dienes and their derivatives as potent 17α-hydroxylase/C17,20-lyase inhibitors or antiproliferative agents depending on the substitution pattern of the heteroring.

A series of novel 17-(4'-formyl)pyrazolylandrosta-5,16-dienes were efficiently synthesized in two steps from pregnadienolone acetate with monosubstituted hydrazines via the cyclization/formylation sequence of the primarily formed hydrazones on treatment with the Vilsmeier-Haack reagent. The products were further transformed by deacetylation and subsequent reduction in order to enlarge the compound library available for pharmacological studies. Moreover, 4'-formylpyrazoles containing H or Me on the heteroring-N were subjected to oxime formation and Ac2O-induced dehydration to furnish the corresponding 4'-cyano derivatives in good yields. The antiproliferative activities of the structurally related steroidal 17-exo-pyrazole derivatives were tested in vitro on four human adherent breast cancer cell lines (MCF7, T47D, MDA-MB-231 and MDA-MB-361): the microculture tetrazolium assay revealed that seven compounds exerted better cell growth-inhibitory effects on some or all these cell lines than those of the reference cisplatin. With regard to the well-known structural features that a potent C17,20-lyase inhibitor should possess, some relevant derivatives were tested in vitro from the aspects of their inhibitory effects on rat testicular enzyme, and one of them proved to exert noteworthy enzyme-inhibitory action, with an IC50 (26 nM) of the same order of magnitude as that of abiraterone.

Inhibition of quorum-sensing signals by essential oils.

The role of quorum sensing (QS) is well known in microbial pathogenicity and antibiotic resistance. QS is responsible for motility, swarming, and biofilm production based on the signal molecules, e.g., acylated homoserine lactones (AHLs) produced by micro-organisms above certain population density. The inhibition of QS may reduce pathogenicity, antibiotic resistance and biofilm formation in systemic and local infections. The homoserine lactones and other transmitters contribute to antibiotic resistance and pathogenicity of several bacteria; consequently the inhibition of QS signals reduces the problem of resistance and virulence. Due to the increasing number of persistent non-treatable infections, there is an urgent need to develop new strategies to combat infections that destabilize bacterial communities in the host. The effect of essential oils on bacterial growth and QS were evaluated using the sensor strain Chromobacterium violaceum CV026 and N-acyl homoserine lactone (AHL) producing Escherichia coli ATTC 31298 and the grapevine colonizing Ezf 10-17 strains. Of the tested oils, rose, geranium, lavender and rosemary oils were the most potent QS inhibitors. Eucalyptus and citrus oils moderately reduced pigment production by CV026, whereas the chamomile, orange and juniper oils were ineffective.

Characterization of intrinsic efflux activity of Enterococcus faecalis ATCC29212 by a semi-automated ethidium bromide method.

Enterococcus faecalis is recognized as a multidrug-resistant nosocomial pathogen. The phenotypic basis for this is largely uncharacterized. The intrinsic efflux system of the antibiotic-susceptible E. faecalis ATCC29212 strain was studied using a semi-automated method that assesses accumulation and efflux of the universal efflux pump substrate ethidium bromide (EB). The results show that the intrinsic efflux system of this Enterococcus strain is controlled by energy derived from the catabolism of glucose and the proton concentration of the medium. At pH 5, agents that inhibit efflux pumps in Gram-positive organisms and the proton gradient un-coupler CCCP do not increase accumulation nor inhibit efflux of EB. In contrast, at pH 8, where the proton concentration is 1,000-fold lower, these agents increase accumulation and efflux of EB. These results are relevant to infections produced by E. faecalis and subsequent antibiotic therapy with antibiotics to which the organism is known to be intrinsically resistant.

Chemoprevention and inhibition of P-glycoprotein in cancer cells by Chinese medicinal herbs.

Many of the herbal extracts used in the Chinese clinical medical routine inhibit the growth of tumor cells. In the present work, extracts of 12 selected herbs were prepared with methanol, chloroform, ethyl acetate and water, and the effects of these on the multidrug resistance (MDR) and P-glycoprotein of mouse lymphoma cells transfected with the human mdr1 gene and on a human lung alveolar epithelial cell line were investigated. The extracts were tested for antiproliferative effects, and the reversal of MDR in mouse lymphoma cells. The possible chemopreventive effect of the chloroform extracts was studied on the expression of cytomegalovirus (CMV) immediate-early (IE) antigen in human lung cancer cells (A549). The antimicrobial effects of the extracts were tested on some representative micro-organisms. Certain of the chloroform extracts of the plant materials were the most effective compounds on the reversal of MDR. Two of the chloroform extracts enhanced the antiproliferative effect of doxorubicin on MDR mouse lymphoma cells. The selected extracts did not show any antibacterial effect with the agar diffusion method. Certain chloroform extracts decreased the intermediate IE antigen expression of CMV in A459 cells.