Design, synthesis and exploration of novel triazinoindoles as potent quorum-sensing inhibitors and radical quenchers.

Background: Antimicrobial resistance has become a critical health concern, and quorum-sensing exacerbates the resistance by facilitating cell-to-cell communication within the microbial community, leading to severe pathogenic outbreaks. Methods & results: Novel 1-(2-((5H-[1,2,4]-triazino[5,6-b]indol-3-yl)thio)acetyl)indoline-2,3-diones were synthesized. The title compounds exhibit outstanding anti-quorum-sensing efficacy, and compound 7g demonstrated the maximum proficiency (IC50 = 0.0504 µg/ml). The hybrids displayed potent antioxidant action, and compound 7c showed the highest antioxidant ability (IC50 = 40.71 µg/ml). Molecular docking of the isatin hybrids against DNA gyrase and quorum-sensing receptor CviR validated the observed in vitro findings. The befitting pharmacokinetic profile of the synthesized drug candidates was ascertained through absorption, distribution, metabolism, excretion and toxicity screening. Conclusion: The remarkable biocompetence of the synthesized triazinoindoles may help to combat drug-resistant infections.

Enhanced Xylanolytic enzyme production from Parthenium hysterophorus through assessment of the RSM tool and their application in saccharification of lignocellulosic biomass.

Parthenium hysterophorous, a widespread weed in India, contributes a substantial amount of lignocellulosic biomass. The key objective of this study is to evaluate the feasibility of producing xylanase enzyme from P. hysterophorus weed biomass using the fungus Aspergillus niger. The impact of various physiological factors was confirmed through a two-step approach: first, a one-factor-at-a-time (OFAT) investigation, and subsequently, employing the RSM-based CCD method in statistical design. This research revealed that the RSM-based model led to the optimization of enzyme activity, resulting in a value of 2098.08 IU/gds for xylanase. This was achieved with an incubation time of 4.5 days, a medium pH of 6, and a cultivation temperature of 32.5 °C. Additionally, a pretreatment involving 1% NaOH and a 30-min autoclave treatment was found to alter the chemical composition of lignocellulose substrates (cellulose 43.87% and xylan 28.7%), thereby enhancing the efficiency of enzymatic hydrolysis. Moreover, fermentable sugars were produced by autoclave-assisted alkali pretreatment (NaOH-1.0% w/v) at rates of 219.6 ± 2.05 mg/gds-1 by utilizing the crude xylanase from A. niger and 291.3 ± 1.2 mg/gds-1 from commercial xylanase enzyme. Our study revealed that P. hysterophorus served as a viable and affordable substrate for fermentable sugar liberation, and xylanase is a rate-limiting enzyme in enzymatic saccharification.

Simultaneous laccase production and transformation of bisphenol-A and triclosan using Trametes versicolor.

New age micro-pollutants, bisphenol-A (BPA) and triclosan (TCA), known for their carcinogenic effects in living organisms can effectively be removed from water using laccase from Trametes versicolor. Laccase was produced from T. versicolor JSRK13 in both submerged and solid-state fermentation (SmF and SSF) conditions. In SmF, T. versicolor JSRK13 gave the maximum production of laccase on the 10th day with an activity of 22 U mL- 1, whereas, in SSF 185 U g- 1 of the enzyme was produced on the 17th day. Maximum production of laccase was observed with Parthenium as substrate. Parthenium, with a particle size of 3-5 mm having 60% moisture was found to be a suitable substrate for laccase production and simultaneous transformation (LPST) of BPA in a synergistic manner. A one-step concentration using 85% ammonium sulphate followed by dialysis was sufficient to give 6.7-fold purification of laccase from the crude culture filtrate. Transformation of BPA was achieved in both SmF and SSF conditions along with the production of laccase, whereas TCA was degraded with free enzyme only. Above 90% of BPA (55-5 mg L- 1) was degraded using the LPST strategy with HBT acting as a mediator in the reaction. LPST strategy did not work for TCA as it completely inhibits the growth of T. versicolor JSRK13. TCA was degraded up to 75% (1.5-0.375 mg L- 1) by the free enzyme. Our study of simultaneous laccase production and transformation proved to be efficacious in case of BPA. The results indicate that industrial and sewage wastewater containing BPA can potentially be treated with T. versicolor JSRK13 laccase. The described strategy can further be used to develop a bioprocess which can work both on solid and liquid wastes containing BPA.

Laccase grafted membranes for advanced water filtration systems: a green approach to water purification technology.

PURPOSE: Conventional wastewater treatment technologies are not good enough to completely remove all endocrine disrupting compounds (EDCs) from the water. Membrane separation systems have emerged as an attractive alternative to conventional clarification processes for waste and drinking water. Coupling of a membrane separation process with an enzymatic reaction has opened up new avenues to further enhance the quality of water. This review article deliberates the feasibility of implementing enzymatic membrane reactors has been deliberated. MATERIALS AND METHODS: A comprehensive study of conventional water treatment technologies was carried out and their shortcomings were pointed out. Research findings from the leading groups working on enzyme grafted membrane based water purification were summarized. This review also comprehends the patent documents pertinent to the technology of enzyme grafted membranes for water purification. RESULTS: Immobilization of an enzyme on a membrane improves the performance of membrane filtration, and processes for the treatment of polluted water. Research has started exploring the potential for laccase enzymes because it can catalyze the oxidation of a wide range of substrates, structurally comparable to EDCs, by a radical-catalyzed reaction mechanism, with corresponding reduction of oxygen to water in an electron transfer process. Further, in the presence of certain mediators, the substrate range of laccases can be further enhanced to non-aromatic substrates. CONCLUSIONS: Removal of EDCs by laccase cross-linked enzyme aggregates in fixed-bed reactors or fluidized-bed reactors and laccase immobilized ultrafiltration (LIUF) membranes are proving their worth in water purification technology. The major operational issues with the use of LIUF membranes are enzyme instability in real wastewater and membrane fouling. In view of the above-stated characteristics, laccases are considered as the most promising enzyme for a greener and less expensive water purification technology.