Evaluation of 1,10-phenanthroline-based hydroxamate derivative as dual histone deacetylases/ribonucleotide reductase inhibitor with antitumor activities.

BACKGROUND: Aberrant expression of histone deacetylases (HDACs) and ribonucleotide reductase (RR) enzymes are commonly observed in various cancers. Researchers are focusing on these enzymes in cancer studies with the aim of developing effective chemotherapeutic drugs for cancer treatment. Targeting both HDAC and RR simultaneously with a dual HDAC/RR inhibitor has exhibited enhanced effectiveness compared to monotherapy in cancer treatment, making it a promising strategy. OBJECTIVES: The objective of the study is to synthesize and assess the anti-cancer properties of a 1,10-phenanthroline-based hydroxamate derivative, characterizing it as a novel dual HDAC/RR inhibitor. METHODS: The N1-hydroxy-N8-(1,10-phenanthrolin-5-yl)octanediamide (PA), a 1,10-phenanthroline-based hydroxamate derivative, was synthesized and structurally characterized. The compound was subjected to in vitro assessments of its anti-cancer, HDAC, and RR inhibitory activities. In silico docking and molecular dynamics simulations were further studied to explore its interactions with HDACs and RRM2. RESULTS: The structurally confirmed PA exhibited antiproliferative activity in SiHa cells with an IC50 of 16.43 µM. It displayed potent inhibitory activity against HDAC and RR with IC50 values of 10.80 µM and 9.34 µM, respectively. Co-inhibition of HDAC and RR resulted in apoptosis-induced cell death in SiHa cells, mediated by the accumulation of reactive oxygen species (ROS). In silico docking studies demonstrated that PA can effectively bind to the active sites of HDAC isoforms and RRM2. Furthermore, PA demonstrated a more favorable interaction with HDAC7, displaying a docking score of -9.633 kcal/mol, as compared to the standard HDAC inhibitor suberoylanilide hydroxamic acid (SAHA), which exhibited a docking score of -8.244 kcal/mol against HDAC7. CONCLUSION: The present study emphasizes the prospect of designing a potential 1,10-phenanthroline hydroxamic acid derivative as a novel dual HDAC and RR-inhibiting anti-cancer molecule.

Thermostable bacterial laccase for sustainable dyeing using plant phenols.

Laccase is regarded as an efficacious eco-friendly enzyme in various industries. Thus, various laccases have been explored to mitigate the environmental effects of conventional industrial processing; however, the prospects of laccase in hair dyeing have not been thoroughly explored to date. On account of the adverse environmental and health-related issues posed by chemical hair dyeing, laccase as a natural alternative in dyeing hair has recently gained attention. In this study, we executed hair dyeing with different colours and shades of hair dyes developed from natural plant phenols, including ferulic acid, gallic acid, catechol, and syringaldehyde, catalysed by a novel thermostable bacterial laccase (LacT) from Brevibacillus agri. The dyed hair was characterised in terms of its colourimetric parameters (L*, a*, and b*), colour strength (K/S), reflectance (R) and colour durability. L* means luminosity and is defined by L* values from 0 (black) to 100 (white). A positive value of a* means red shades and a negative value indicates green shades. A positive value of b* shows yellow shades and a negative value indicates blue shades. Optical microscopy of circular and longitudinal sections of the dyed hair revealed that the laccase-catalysed dyes did not merely stick to the surface; instead, they well-penetrated the hair. Furthermore, the dyeing process did not affect the surface morphology of the dyed hair. The dyed hair also exhibited a desirable range of colour diversity in terms of market-driven demands and showed considerable resistance to fading during shampooing and pH alterations. Post-dyeing, the texture and tensile strength of the dyed hair remained nearly unchanged. Overall, the outcomes suggest that LacT holds high potential to be exploited extensively in the hair dyeing industry as an alternative to chemical hair dyes.

Laccases: Thriving the domain of bio-electrocatalysis.

Laccases have been in the spotlight due to its capability to catalyse electrocatalytic reactions. The Its ability to reduce water to oxygen has made it more bio-compatible than majority of electrocatalysts. The exploitation of such biocatalysts via protein engineering and biotechnological techniques have rendered a significant breakthrough in the field of electrocatalysis. This review aims to provide a comprehensive overview of the various laccase-driven electrocatalytic reactions. Structural and functional features of laccases that contribute towards the electron transfer mechanism and reduction potential have been meticulously described. Tailoring of laccase affords an excellent prospect for its application in diverse fields like, biocathode fabrication for enzymatic biofuel cells, biosensors, and electrocatalytic reactions like water splitting. The substantial knowledge of enzyme engineering, primarily through site directed mutagenesis is propitious for the design of optimal bioelectrocatalyst. This review seeks to provide an insight for the optimisation of electrocatalytic properties of laccase thereby broadening the horizon for the development of resilient and biocompatible bioelectrocatalyst.