Novel quaternary ammonium compounds derived from aromatic and cyclic amino acids: Synthesis, physicochemical studies and biological evaluation.

Novel quaternary ammonium surfactants (QUATs) derived from phenylalaninyl-proline dipeptide with chain length C12 and C14 were synthesised as potential active ingredients to be used in body cleansing formulations. The physicochemical properties and biological activities of the QUATs were determined in both single and in mixed surfactant system with either the conventional anionic surfactant sodium dodecyl sulphate (SDS) or sodium N-dodecyl prolinate. The C12 QUAT derivative showed antagonistic behaviour in both SDS and sodium N-dodecyl prolinate mixed surfactant system. Comparing the mixed system of the C12 QUAT with SDS and sodium N-dodecyl prolinate, it was found that the latter displayed better antibacterial activity together with the lower ocular irritation. The C12 QUAT-sodium N-dodecyl prolinate mixture were non cytotoxic at a concentration corresponding to its MIC value, showing that the mixture was selective towards bacterial cells rather than mammalian cell lines. Diffusion measurements showed that the sodium N-dodecyl prolinate surfactant consisted of 26 molecules per micelle in water but only 3 molecules per micelle in DMSO/water (1:1). On the other hand, C12 QUAT did not form a micelle in DMSO/Water. Membrane permeability studies of the C12 QUAT and sodium N-dodecyl prolinate showed that these surfactants are capable to penetrate into deeper skin layers to exert their antibacterial and cleansing action and hence can be used as a promising candidate as active ingredients in body wash formulations.

Synthesis and biological properties of a series of aryl alkyl disulfide derivatives.

Disulfide containing compounds are recognized for their wide range of biological properties and are known for their important applications in the pharmaceutical field. In this study, a series of diaryl disulfides with varying alkyl chain length (C8-C16) was synthesized and assessed for their physicochemical and biological properties. The interactions of compounds with bovine serum albumin (BSA) was investigated in order to study their ability to bind with blood serum protein. An increase in the binding constants (Ka) was observed with increasing chain length C8-C12, while a decrease in value was obtained with compounds of chain length C14 and C16 showing a cut off effect at C12. The thermodynamic parameters of binding indicated that the compounds bound to BSA mostly by van der Waals forces and hydrogen bonding. Molecular docking studies showed that the diaryl disulfides displayed greater binding affinity to Trp 213 rather than the Trp 134 residue on the BSA molecule. The trend observed in molecular docking is in line with the fluorescence binding studies whereby the C12 derivative was found to show optimum affinity with BSA. The disulfide with chain length C10 showed moderate antibacterial activity the highest inhibitory activity against Bacillus cereus. The cytotoxicity of the disulfides towards HaCaT cells decreased from C8 to C14. The overall results obtained show that these disulfides have potent antibacterial properties against Gram-positive bacteria Bacillus cereus at concentrations which are relatively non-toxic to normal cells.

Antiplasmodial Diterpenoids from Psiadia arguta.

An ethyl acetate extract of Psiadia arguta leaves showed in vitro antiplasmodial activity against Plasmodium falciparum with IC50 values of 12.3 ± 2.4 µg/mL (3D7 strain) and 13.5 ± 3.4 µg/mL (W2 strain). Phytochemical investigation led to the isolation and characterization of 16 compounds including four new diterpenoids: labdan-8α-ol-15-yl-(formate) (1), labdan-8α-ol-15-yl-(2-methylbutanoate) (2), labdan-8α-ol-15-yl-(3-methylpentanoate) (3), and labdan-8α-ol-15-yl-(labdanolate) (4). The latter compounds were characterized by spectroscopic methods (1D and 2D NMR, HRMS, and IR). The in vitro antiplasmodial activities of all compounds were evaluated. The known compounds labdan-13( E)-en-8α-ol-15-yl acetate (5), labdan-8α-ol-15-yl acetate (6), 13- epi-sclareol (7), labdan-13( E)-ene-8α,15-diol (8), and (8 R,13 S)-labdane-8α,15-diol (9) exhibited antiplasmodial effects, with IC50 values of 29.1, 33.2, 35.0, 36.6, and 22.2 µM, respectively.

The genus Psiadia: Review of traditional uses, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Psiadia Jacq. ex. Willd. belongs to the Asteraceae family and includes more than 60 species. This genus grows in tropical and subtropical regions, being especially well represented in Madagascar and the Mascarene Islands (La Réunion, Mauritius and Rodrigues). Several Psiadia species have been used traditionally for their medicinal properties in Africa and the Mascarene Islands. Based on traditional knowledge, various phytochemical and pharmacological studies have been conducted. However there are no recent papers that provide an overview of the medicinal potential of Psiadia species. Therefore, the aim of this review is to provide a comprehensive summary of the botany, phytochemistry and pharmacology of Psiadia and to highlight the gaps in our knowledge for future research opportunities. MATERIALS AND METHODS: The available information on traditional uses, phytochemistry and biological activities of the genus Psiadia was collected from scientific databases through a search using the keyword 'Psiadia' in 'Google Scholar', 'Pubmed', 'Sciencedirect', 'SpringerLink', 'Web of Science', 'Wiley' and 'Scifinder'. Additionally, published books and unpublished Ph.D. and MSc. dissertations were consulted for botanical information and chemical composition. RESULTS: Historically, species of the genus Psiadia have been used to treat a wide range of ailments including abdominal pains, colds, fevers, bronchitis, asthma, rheumatoid arthritis, skin infections and liver disorders among others. Phytochemical works led to the isolation of flavonoids, phenylpropanoids, coumarins and terpenoids. Furthermore, phytochemical compositions of the essential oils of some species have been evaluated. Crude extracts, essential oils and isolated molecules showed in vitro pharmacological activities, such as antimicrobial, anti-viral, anti-inflammatory, antiplasmodial and antileishmanial activities. Crude extracts of Psiadia dentata and Psiadia arguta have specifically been found to be potentially useful for inhibition of growth of Plasmodium falciparum. However, pharmacological data on this particular genus is quite limited. Further research is necessary to determine the active compounds and the underlying mechanisms.

Synthesis, micellisation and interaction of novel quaternary ammonium compounds derived from l-Phenylalanine with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine as model membrane in relation to their antibacterial activity, and their selectivity over human red blood cells.

A series of quaternary ammonium compounds (QUATS) derived from l-Phenylalanine have been synthesized and their antibacterial efficiencies were determined against various strains of Gram-positive and Gram-negative bacteria. The antibacterial activity increased with increasing chain length, exhibiting a cut-off effect at C14 for Gram-positive and C12 for Gram-negative bacteria. The l-Phenylalanine QUATS displayed enhanced antibacterial properties with a higher cut-off point compared to their corresponding l-Phenylalanine ester hydrochlorides. The CMC was correlated with the MIC, inferring that micellar activity contributes to the cut-off effect in antibacterial activity. The hemolytic activities (HC50) of the QUATS against human red blood cells were also determined to illustrate the selectivity of these QUATS for bacterial over mammalian cells. In general, the MIC was lower than the HC50, and assessment of the micellar contribution to the antibacterial and hemolytic evaluation in TBS as a common medium confirmed that these QUATS can act as antibacterial, yet non-toxic molecules at their monomer concentrations. The interaction of the QUATS with the phospholipid vesicles (1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC) in the presence of 1-anilino-8-naphthalene sulfonate (ANS) and 1,6-diphenyl-1,3,5-hexatriene (DPH) as fluorescence probes showed that the presence of the quaternary ammonium moiety causes an increase in hydrophobic interactions, thus causing an increase in antibacterial activity.

A study of the antibacterial activity of L-phenylalanine and L-tyrosine esters in relation to their CMCs and their interactions with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC as model membrane.

Cationic amino acid-based surfactants are known to interact with the lipid bilayer of cell membranes resulting in depolarization, lysis and cell death through a disruption of the membrane topology. A range of cationic surfactant analogues derived from L-Phenylalanine (C1-C20) and L-Tyrosine (C8-C14) esters have been synthesized and screened for their antibacterial activity. The esters were more active against gram positive than gram negative bacteria. The activity increased with increasing chain length, exhibiting a cut-off effect at C12 for gram positive and C8/C10 for gram negative bacteria. The cut-off effect for gram negative bacteria was observed at a lower alkyl chain length. The CMC was correlated with the MIC, inferring that micellar activity contribute to the cut-off effect in antibacterial activity. The interaction of the cationic surfactants with the phospholipid vesicles (1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC) in the presence of 1-anilino-8-naphthalene sulfonate (ANS) and 1,6-diphenyl-1,3,5-hexatriene (DPH) as fluorescence probes showed that an increase in ionic interaction causes an increase in antibacterial activity. Increase in hydrophobic interaction increases the antibacterial activity only to a certain chain length, attributing to the cut-off effect. Therefore, both electrostatic and hydrophobic interactions, involving the polar and nonpolar moieties are of paramount importance for the bactericidal properties.

Three anilides of 2,2'-thiodibenzoic acid.

The structures of N,N'-bis(2-methylphenyl)-2,2'-thiodibenzamide, C(28)H(24)N(2)O(2)S, (Ia), N,N'-bis(2-ethylphenyl)-2,2'-thiodibenzamide, C(30)H(28)N(2)O(2)S, (Ib), and N,N'-bis(2-bromophenyl)-2,2'-thiodibenzamide, C(26)H(18)Br(2)N(2)O(2)S, (Ic), are compared with each other. For the 19 atoms of the consistent thiodibenzamide core, the r.m.s. deviations of the molecules in pairs are 0.29, 0.90 and 0.80 Å for (Ia)/(Ib), (Ia)/(Ic) and (Ib)/(Ic), respectively. The conformations of the central parts of molecules (Ia) and (Ib) are similar due to an intramolecular N-H···O hydrogen-bonding interaction. The molecules of (Ia) are further linked into infinite chains along the c axis by intermolecular N-H···O interactions, whereas the molecules of (Ib) are linked into chains along b by an intermolecular N-H···π contact. The conformation of (Ic) is quite different from those of (Ia) and (Ib), since there is no intramolecular N-H···O hydrogen bond, but instead there is a possible intramolecular N-H···Br hydrogen bond. The molecules are linked into chains along c by intermolecular N-H···O hydrogen bonds.

In vitro anti-glycation and anti-oxidant properties of synthesized Schiff bases.

A series of mono, bis and mixed Schiff bases (1-7) were synthesised and evaluated for potential anti-glycation and anti-oxidant activities using the bovine serum albumin-glucose assay and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical assay respectively. All compounds showed significant (p<0.05) antiglycating activities with IC50 values (4.02x10(-24)±0.1-2.88x10(-1)±1.35 mM) which were lower than the standard positive control aminoguanidine (IC50: 1.51x10(-3)±2.11 mM). Moreover, compounds 1-7 were found to possess significant (p<0.05) DPPH radical scavenging properties with SC50 values (1.31x10(-19)±0.05 to 2.25x10(-1)±1.24 mM) lower than the standard ascorbic acid (SC50: 5.50x10(-3)±2.11 mM). Compound 6 was found to be the most potent anti-glycating molecule (IC50 value: 4.02x10(-24)±0.1 mM) while compound 5 was the most potent anti-oxidant molecule (SC50: 1.31x10(-19)±0.05 mM); both being significantly lower (p<0.05) than the respective positive controls used. The present data showed that the number of phenolic OH together with structural changes influence both the anti-glycation and anti-oxidant observed herein. This study provides for the first time a series of potential template molecules for possible pharmaceutical applications that warrant further investigation as potential anti-glycation and anti-oxidant agents which could be of importance in metabolic diseases including diabetes mellitus.

New lobane and cembrane diterpenes from two comorian soft corals.

Preliminary biological investigation of a collection of Comorian soft corals resulted in the selection of two specimens, one of Sarcophyton and the other of Lobophytum, on the basis of their toxicity on larvae of the brine shrimp (Artemia salina) and inhibition of acetylcholinesterase, respectively. Bioassay-guided fractionations provided a known antitumor promoter cembrane diterpenoid, (+)-sarcophytol-A (1), along with a new lobane diterpenoid, carbomethoxyfuscol (2), from Sarcophyton sp., and a new cembranoid, crassumolide E (3), from Lobophytum sp. The structures of compounds 1-3 were determined by spectroscopic analysis and by comparison of the spectral data with previously reported values. The cembranoid 3 was found to exhibit a moderate inhibitory effect on acetylcholinesterase.

N,N'-Bis(3-phenyl-prop-2-en-1-yl-idene)-2,2'-disulfanediyldianiline.

In the title compound, C(30)H(24)N(2)S(2), the two phenyl rings attached to the S atoms are oriented nearly perpendicularly, making a dihedral angle of 86.14 (8)°. Each of the two ArCH=CHCH=N units is almost planar, having maximum deviations from the least-squares planes of 0.125 and 0.149 Å, and rotated around the C-N bonds relative to the adjacent phenyl ring by 110.26 and 30.30°.

Quantification of alcohol in beverages by density and infrared spectroscopy methods.

The amount of ethanol in beverages has been quantified by density and infrared spectroscopy methods. The density method allows only the amount of ethanol to be quantified, while the infrared spectroscopy method allows the quantification of ethanol and, if any, the presence of contaminants such as methanol. The amount of ethanol quantified agrees to bottle declaration particularly for the infrared spectroscopy method. The infrared spectroscopy method coupled with a mathematical treatment (PCA and PLS-2) thus distinguishes itself as a fast and reliable technique for determining the amount of ethanol in beverages.