Molecular Design of Potential Triple-Action Antibacterial Agents and Related Pro-Drugs

 บทคัดย่อ การเพิ่มขึ้นของเชื้อแบคทีเรียดื้อยาที่ก่อโรคในมนุษย์เป็นปัญหาด้านสุขภาพทั่วโลก ความท้าทายในการแก้ปัญหานี้ทำให้มีการเพิ่มความพยายามในการวิจัยแบบสหสาขาวิชามากขึ้น หนึ่งในความพยายามนั้นคือการพัฒนาโมเลกุลของสารยับยั้งเชื้อแบคทีเรียดื้อยาให้มีการออกฤทธิ์ยับยั้งเชื้อได้มากกว่าหนึ่งเป้าหมายในเซลล์ของแบคทีเรีย บทความนี้ได้กล่าวครอบคลุมถึงสิ่งที่ต้องพิจารณาในการออกแบบโมเลกุล   ความเป็นไปได้ในการสังเคราะห์สารยับยั้งเชื้อแบคทีเรียที่ในโมเลกุลเดียวกันสามารถเกิดอันตรกิริยากับเป้าหมายในเซลล์ของแบคทีเรียได้ถึงสามเป้าหมายและออกฤทธิ์ร่วมกันอย่างมีประสิทธิภาพในการยับยั้งเชื้อแบคทีเรีย และกล่าวถึงสารโปร-ดรักส์ของสารยับยั้งเชื้อแบคทีเรียดังกล่าว โดยเฉพาะอย่างยิ่งการออกแบบและการสังเคราะห์สารยับยั้งเชื้อแบคทีเรียที่มีโครงสร้างของสารอัลคาลอยด์เบอร์เบอรีนเป็นองค์ประกอบ  - - - Molecular Design of Potential Triple-Action Antibacterial Agents and Related Pro-DrugsABSTRACT Increasing antibiotic resistance by human pathogenic bacteria is a global health concern.  This health challenge calls for increased multi-disciplinary research efforts to address the issue and one such effort is concerned with the development of novel single molecule agents with more than one bacterial target site for action or interaction. This review covers molecular design considerations and some possible synthetic molecular entities for potential triple-action antibacterial agents and related pro-drugs, particularly those based on the quaternary alkaloid berberine

Biosorption of lac dye by the red marine alga Gracilaria tenuistipitata: biosorption kinetics, isotherms, and thermodynamic parameters

The hypothesis that the dried, ground biomass of the red marine alga Gracilaria tenuistipitata could be used for the efficient removal of lac dye from aqueous solution was assessed in this work. The effects of parameters such as initial pH, biosorbent dosage, contact time, initial dye concentration, and temperature on the biosorption capacity of the dye were investigated. Equilibrium data were analysed using Langmuir, Freundlich, and Temkin isotherm models, and the Freundlich model provided the highest coefficient of determination values. Biosorption kinetic data were successfully described with a pseudo-second-order model at initial dye concentrations of 50, 80, 100, and 120 mg l−1. The thermodynamic parameters of biosorption - enthalpy change (∆H° = −30.64 kJ mol−1), free energy change (∆G° = 4.32 kJ mol−1 at 303 K to 7.78 kJ mol−1 at 333 K), and entropy change (∆S° = −115.38 J mol−1 K−1) - were determined. The negative value of the enthalpy change and positive values of the free energy change indicate that the biosorption process is exothermic and non-spontaneous. The negative value of the entropy change is consistent with decreased randomness at the solid-liquid interface with dye biosorption. Attenuated total reflectance-Fourier transform infrared spectroscopic analysis confirmed the presence of lac dye on the G. tenuistipitata material. The efficiency of lac dye removal by this biomass material at 20 g l−1 and with an initial dye concentration of 50 mg l−1 in acidic solution was 71%, which indicated its potential usefulness as a new dye biosorbent

The Flavonoids of Orophea polycarpa A. DC. (Annonaceae)

Investigation on the neutral fraction of the leaves of Oraphea polycarpa A. DC. led to the isolation of two flavonoids identified as 2'-hydroxy-4,4',6'trimethoxychalcone and 5,7,4'-trimethoxyflavanone

Additive effects on cotton dyeing with dye extract from achiote seeds

466-474Cotton yarns have been pretreated with the additives, such as chitosan, microcrystalline chitosan, quaternized chitosan & aqueous extract from the fruit of Diospyros mollis Griff, as well as with the commercial formaldehyde-free cationic fixing agent (Sera® Fast C-NC) & alum (post-mordanting), and their dyeing fastness properties are studied. These treated cotton yarns are then dyed with the annatto dye extract from Bixa orellana L. (Achiote) seeds and tested for different properties including K/S value, light fastness, and wash fastness. Pre-treatment of cotton yarn with chitosan or microcrystalline chitosan solution (together with glyoxal cross-linking) or quaternized chitosan, or Sera® Fast C-NC before dyeing, shows a better color depth (K/S) and improved wash fastness properties in comparison to yarn with alum post-mordanting and the untreated cotton yarn. Improved light fastness is also obtained on inclusion of the anti-oxidant ascorbic acid in the post-treatment protocol. These additive treatments thus offer considerable potential for the improved annatto dyeing of cotton

A convenient and efficient synthesis of (S)-lysine and (S)-arginine homologues via olefin cross-metathesis

A convenient five step synthesis of (S)-homolysine, incorporating a key olefin cross-metathesis step in the chain extension methodology, has been developed, together with a six step related synthesis of a new homologue of arginine, (S)-bishomoarginine

Additive effects on cotton dyeing with dye extract from achiote seeds

Cotton yarns have been pretreated with the additives, such as chitosan, microcrystalline chitosan, quaternized chitosan &aqueous extract from the fruit of Diospyros mollis Griff, as well as with the commercial formaldehyde-free cationic fixingagent (Sera® Fast C-NC) & alum (post-mordanting), and their dyeing fastness properties are studied. These treated cottonyarns are then dyed with the annatto dye extract from Bixa orellana L. (Achiote) seeds and tested for different propertiesincluding K/S value, light fastness, and wash fastness. Pre-treatment of cotton yarn with chitosan or microcrystallinechitosan solution (together with glyoxal cross-linking) or quaternized chitosan, or Sera® Fast C-NC before dyeing, shows abetter color depth (K/S) and improved wash fastness properties in comparison to yarn with alum post-mordanting and theuntreated cotton yarn. Improved light fastness is also obtained on inclusion of the anti-oxidant ascorbic acid in the posttreatmentprotocol. These additive treatments thus offer considerable potential for the improved annatto dyeing of cotton

A mass spectrometric investigation of novel quadruplex DNA-selective berberine derivatives

ESI mass spectrometry was used to assess the binding of 13-substituted, 5-nitro-2-phenylindolyl- and 2-naphthalenyl-based berberine derivatives to inter- and intramolecular G-quadruplex DNA molecules. In contrast with the parent berberine, the compounds showed selectivity for quadruplex over duplex DNA and stabilised the quadruplex structure. They represent a new class of quadruplex DNA-selective ligands. © 2010 The Royal Society of Chemistry

Attaching NorA efflux pump inhibitors to methylene blue enhances antimicrobial photodynamic inactivation of Escherichia coli and Acinetobacter baumannii in vitro and in vivo

Resistance of bacteria to antibiotics is a public health concern worldwide due to the increasing failure of standard antibiotic therapies. Antimicrobial photodynamic inactivation (aPDI) is a promising non-antibiotic alternative for treating localized bacterial infections that uses non-toxic photosensitizers and harmless visible light to produce reactive oxygen species and kill microbes. Phenothiazinium photosensitizers like methylene blue (MB) and toluidine blue O are hydrophobic cations that are naturally expelled from bacterial cells by multidrug efflux pumps, which reduces their effectiveness. We recently reported the discovery of a NorA efflux pump inhibitor-methylene blue (EPI-MB) hybrid compound INF55-(Ac)en-MB that shows enhanced photodynamic inactivation of the Gram-positive bacterium methicillin-resistant Staphylococcus aureus (MRSA) relative to MB, both in vitro and in vivo. Here, we report the surprising observation that INF55-(Ac)en-MB and two related hybrids bearing the NorA efflux pump inhibitors INF55 and INF271 also show enhanced aPDI activity in vitro (relative to MB) against the Gram-negative bacteria Escherichia coli and Acinetobacter baumannii, despite neither species expressing the NorA pump. Two of the hybrids showed superior effects to MB in murine aPDI infection models. The findings motivate wider exploration of aPDI with EPI-MB hybrids against Gram-negative pathogens and more detailed studies into the molecular mechanisms underpinning their activity

Can Teachers Accurately Predict Student Performance?

In two studies, we examined the effect of professional development to improve mathematics instruction on the accuracy of teachers\u27 monitoring of student learning. Study 1 was conducted with 36 teachers participating in three years of professional development. Judgment accuracy was influenced by the fidelity with which what was learned in the professional development. Study 2 was conducted with 64 teachers from 8 schools, which were randomly assigned to receive professional development or serve as a control. Judgment accuracy was greater for teachers receiving professional development than for teachers who did not and teachers were better to predict students\u27 computational skills