Novel fatty acid-thiadiazole derivatives as potential antimycobacterial agents.

The discovery of antibiotics around the middle twentieth century led to a decrease in the interest in antimycobacterial fatty acids. In order to re-establish the importance of naturally abundant fatty acid, a series of fatty acid-thiadiazole derivatives were designed and synthesized based on molecular hybridization approach. In vitro antimycobacterial potential was established by a screening of synthesized compounds against Mycobacterium tuberculosis H37Rv strain. Among them, compounds 5a, 5d, 5h, and 5j were the most active, with compound 5j exhibiting minimum inhibitory concentration of 2.34 µg/ml against M.tb H37Rv. Additionally, the compounds were docked to determine the probable binding interactions and understand the mechanism of action of most active molecules on enoyl-acyl carrier protein reductases (InhA), which is involved in the mycobacterium fatty acid biosynthetic pathway.

Transferrin conjugates of antitubercular drug isoniazid: Synthesis and in vitro efficacy.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) has become the world's leading killer disease due to a single infectious agent which survives in the host macrophage for the indefinite period. Hence, it is necessary to enhance the efficacy of the clinically existing antitubercular agents or to discover new anti antitubercular agents. Here, we report the synthesis, characterization and antimycobacterial evaluation of protein-drug conjugates. A carrier protein, Transferrin (Tf) was covalently conjugated to isoniazid (INH) utilizing hydrazone and amide linkers. The purity of the reactions was confirmed by SDS-PAGE while conjugation was confirmed by UV-visible spectrophotometry, MALDI-TOF analysis, and FTIR spectrophotometry. The in vitro antitubercular assay result showed that the inhibitory activity of the parent drug was conserved in both the conjugates. The conjugates were effective against intracellular Mtb H37Rv and were devoid of cytotoxic effect at therapeutic concentration.

Chitosan coated calcium alginate beads for covalent immobilization of acrylamidase: Process parameters and removal of acrylamide from coffee.

This study reports on removal of acrylamide from roasted coffee by acrylamidase from Cupriavidus oxalaticus ICTDB921. Chitosan coated calcium alginate beads were functionalized with citric acid as nontoxic cross linker and activated by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) (1.66:1 w/w) for covalent immobilization of acrylamidase. The optimum beads were obtained using 5% sodium alginate, 1.5% chitosan, and 0.6 mol/L citric acid. The beads prepared at each step were characterized by FTIR and SEM. Coating of chitosan matrix on calcium alginate beads enhanced the mechanical stability over that of calcium alginate and/or chitosan. The immobilized acrylamidase showed optimum pH/temperature of 8.5/65 °C, improved pH/thermal/shelf stability, and retained 80% activity after four cycles. Haldane model could describe the degradation kinetics of acrylamide in batch study. In packed bed column, a bed height, feed flow rate and inlet acrylamide concentration of 20 cm, 1 mL/min, and 100 mg/L gave best results.

Chitosan based copolymer-drug conjugate and its protein targeted polyelectrolyte complex nanoparticles to enhance the efficiency and specificity of low potency anticancer agent.

The effective delivery of low potency anticancer drug is a major challenge. The present study introduces the novel chitosan-polylactic acid (CS-PLA)-drug conjugate and its transferrin receptor targeted polyelectrolyte complex nanoparticles (PEC Nps), encapsulating free drug to increase its potency and specificity. The model drug curcumin (CR) was used and incorporated in this system in both conjugated and encapsulated form. The synthesis of CS-PLA-CR copolymer was confirmed by 1H NMR, FTIR, UV-visible spectrum, DSC thermogram and zeta potential. Further, the nanoparticles engulfing free CR, with average 340 nm particle sizes, were prepared through simple ionic gelation technique utilizing positive charges on copolymer by polyanion sodium alginate (CS-PLA-CR/SA PEC Nps). The prepared Nps showed the high CR content of over 92% with extended period of CR release (60% and 85% at pH 7.4 and 5 respectively even after 8 days). The results were compared with the unmodified CS (without PLA) as a control to understand the effect of PLA side chain. Transferrin (Tf) conjugation on PEC Nps displayed superior cytotoxicity and cellular uptake compared to non-targeted Nps on MCF-7 cell line. Thus, CR loaded Tf-CS-PLA-CR/SA PEC Nps may provide an efficient and targeted delivery for cancer treatment.