Synthesis and antimicrobial activity of 3-arylamino-1-chloropropan-2-ols

A series of nine 3-arylamino-1-chloropropan-2-ols 2a-2i were synthesized and their anti-fungal activity against pathogenic strains of Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger and Candida albicans, and antibacterial activity against four pathogenic bacterial strains of Salmonella typhi, Pseudomonas aeruginosa, Streptococcus pneumonae and Staphylococcus aureus were evaluated using different assay systems. 1-Chloro-3-(4'-chlorophenylamino)-propan-2-ol was found to be the most active anti-fungal compound against three pathogenic strains under study, i.e., A. fumigatus, A. flavus and A. niger; the compound showed more than 90% inhibition of growth of A. fumigatus at a concentration of 5.85 microg/ml in disc diffusion assay. Interestingly, 1-chloro-3-(4'-chlorophenylamino)-propan-2-ol did not show any toxicity up to a concentration of 4000 microg/ml. Although 1-chloro-3-(4'-chlorophenylamino)-propan-2-ol was about 8 times less active than the standard compound amphotericin B, its toxicity was many more fold less than the toxicity of amphotericin B. Further, 1-chloro-3-(2',6'-dichlorophenylamino)-propan-2-ol and 1-chloro-3-(3',5'-dichlorophenylamino)-propan-2-ol were found to be the most active compounds against C. albicans. In the anti-microbial assay, 1-chloro-3-(2',4'-dichlorophenylamino)-propan-2-ol and 1-chloro-3-(3',5'-dichlorophenylamino)-propan-2-ol were found to be the most active compounds against Salmonella typhi and 1-chloro-3-(3',4'-dichlorophenylamino)-propan-2-ol was found to be the most active compound against P. aeruginosa. Although, the activities of 1-chloro-3-(2',4'-dichlorophenylamino)-propan-2-ol and 1-chloro-3-(3',5'-dichlorophenylamino)-propan-2-ol are about half the activity of the standard anti-bacterial compound tetracycline, these compounds also were many fold less toxic than the standard drug.     

Synthesis and bioevaluation of hybrid 4-aminoquinoline triazines as a new class of antimalarial agents

The emergence and rapid spread of chloroquine resistant strains of Plasmodium falciparum has dramatically reduced the chemotherapeutic options. Towards this goal, a series of new class of hybrid 4-aminoquinoline triazines were synthesized and screened against CQ sensitive strain 3D7 of P. falciparum in an in vitro model. Compounds 65 and 69 exhibited more than 99% suppression on day 4 and on day 6 post treatment, compound 69 showed impressive 99.11% suppression against CQ resistant strain N-67 of P. yoelii in an in vivo assay.     

Evidence for tyrosinase as a beta1,6 branch containing glycoprotein: substrate of GnT-V

Tyrosinase is a rate-limiting enzyme in mammalian melanogenesis, and is known as a glycoprotein. Post-translational processing of mammalian tyrosinase is required for its folding, sorting, and for enzymatic activity. Here we show for the first time that the mammalian tyrosinase has beta1,6-branched N-glycan structure that can be recognized by binding with specific lectin Leukoagglutinating phytohematoagglutinin (L-PHA). Further, this specific glycoconjugate structure has been shown to have a function relationship in melanin synthesis.     

Mass spectrometry analysis for the determination of side reactions for cyclic peptides prepared from an Fmoc/t}Bu/Dmab protecting group strategy

The Association of Biomolecular Resource Facilities (ABRF) Peptide Synthesis Research Group (PSRG) proposed for their annual study that laboratory members prepare cyclo(Tyr-Glu-Ala-Ala-Arg-DPhe-Pro-Glu-Asp-Asn) according to the following synthetic pathway: (i) side-chain anchoring Fmoc-Asp(OH)-ODmab to a Rink amide resin; (ii) linear assembly; (iii) Dmab and Fmoc removal, respectively; (iv) on-resin cyclization with an uronium-based coupling reagent; (v) final cleavage/deprotection with TFA. Based upon this protocol, a variety of side-products were identified:(i) N-terminal guanidine formation; (ii) C-terminal piperidyl amide formation; and (iii) a novel C-terminal benzyl amide-guanidine derivative that formed due to a chemical reaction between the Dmab protecting group and the uronium-based coupling agent. The elemental composition and subsequent structure determination of this unexpected derivative was established by tandem mass spectrometry, i.e. low energy collision-induced dissociation experiments with fragment mass determination within 5 ppm.     

Continuous-flow fluoro-immunosensor for paclitaxel measurement

A fluorescence-based continuous-flow immunosensor for sensitive, precise, accurate and fast determination of paclitaxel was developed. The sensor utilizes anti-paclitaxel antibody immobilized through its Fc region and crosslinked by dimethylpimelimidate to protein A attached covalently onto the silanized inner walls of a glass capillary column followed by saturation of the paclitaxel-binding sites with rhodamine-labeled paclitaxel. The assay is based on the displacement and detection downstream of the rhodamine-labeled paclitaxel, by a flow-through spectrofluorometer, as a result of the competition with paclitaxel introduced as a pulse into the stream of carrier buffer flowing through the system. The peak height of the fluorescence intensity profile of the displaced rhodamine-labeled paclitaxel was directly proportional to the concentration of paclitaxel applied and was a function of the carrier buffer flow rate. The sensitivity of the immunosensor response ranged from 0.31 relative fluorescence units (RFU)/ng/ml at a flow rate 0.1 ml/min to 0.52 RFU/ng/ml at 1 ml/min, while the lower detection limit ranged from 1 ng/ml at 0.1 ml/min to 4 ng/ml at 1 ml/min. The immunosensor response was very reproducible (RSD=4.8%; n=10) and linear up to 100 ng/ml. The assay time ranged from 2 min at 1 ml/min to 8 min at 0.1 ml/min. A technique developed to resaturate the antigen binding sites of the immobilized antibody with rhodamine-labeled paclitaxel was successful in regenerating the capillary column without affecting its performance, thus enhancing the economic viability of the immunosensor. The immunosensor was successfully applied for the determination of paclitaxel in human plasma.     

Mechanisms for solubilization of cobalt,copper and nickel from Indian Ocean nodules at near neutral pH by a marine isolate

Polymetallic ocean nodules offer an alternative source for extracting valuable strategic metals like Cu, Co and Ni. A novel biodissolution process was carried out, employing the cell-free spent growth medium from a marine organism (Bacillus M1) isolated from nodules; and Cu, Co and Ni solubilization from the nodules was observed to be beyond the theoretical solubility limits at near neutral pH. Different characterization techniques revealed the presence of phenolic substances in the spent growth medium, which might have formed soluble complexes with the transition metals. The low prevailing E_h redox value in the medium suggested a strong reducing environment, favoring the reductive dissolution of the oxides. A correlation study of dissolution of Cu, Co and Ni with that of Mn and Fe in the nodules was made to investigate the mechanisms of metal solubilization by the marine isolate. Under the influence of a strong reducing environment coupled with complexation by a phenolic substance present in the spent growth medium, Mn and Fe oxides were solubilized from the nodules, resulting in concomitant dissolution of Cu, Co and Ni associated with them in the nodules.