Genome replication is a crucial and essential process for the continuity of life.In all organisms
it starts at a specific region of the genome known as origin of replication (Ori) site. The number of
Ori sites varies in prokaryotes and eukaryotes. Replication starts at a single Ori site in bacteria, but
in eukaryotes multiple Ori sites are used for fast copying across all chromosomes. The situation becomes
complex in archaea, where some groups have single and others have multiple origins of replication.
Themococcales, are a hyperthermophilic order of archaea. They are anaerobes and heterotrophs-peptide
fermenters, sulphate reducers, methanogens being some of the examples of metabolic types. In this paper
we have applied a combination of multiple in silico approaches - Z curve, the cell division cycle (cdc6)
gene location and location of consensus origin recognition box (ORB) sequences for location of origin of
replication in Thermococcus onnurineus, Thermococcus gammatolerans and
other Themococcales and compared the results to that of the well-documented case of Pyrococcus
abyssi. The motivation behind this study is to find the number of Ori sites based on the data
available for members of this order. Results from this in silico analysis show that the Themococcales
have a single origin of replication.
Hyper-pigmentation conditions may develop due to erroneous melanogenesis cascade which leads to excess melanin production. Recently, inhibition of tyrosinase is the main focus of investigation as it majorly contributes to melanin production. This inhibition property can be exploited in medicine, agriculture, and in cosmetics. Present study aims to find a natural and safe alternative molecule as tyrosinase inhibitor. In this study, human tyrosinase enzyme was modelled due to unavailability of its crystal structure to look into the degree of efficacy of glabridin and its 15 derivatives as tyrosinase inhibitor. Docking was performed by
Autodock Vina
at the catalytic core enzyme. Glabridin effects on melanoma cell lines was also elucidated by analysing cytotoxicity and effect on melanin production. Computational ADME analysis was done by SwissADME. Molecular dynamic simulation was also performed to further evaluate the interaction profile of these molecules and kojic acid (positive inhibitor) with respect to apo protein. Notably, four derivatives 5′-formylglabridin, glabridin dimer, 5′-prenyl glabridin and R-glabridin exhibited better binding affinity than glabridin. Glabridin effectively inhibited melanin production in a dose dependent manner. Among these, 5′-formylglabridin displayed highest binding affinity with docking score − 9.2 kcal/mol. Molecular properties and bioactivity analysis by Molinspiration web server and by SwissADME also presented these molecules as potential drug candidates. The study explores the understanding for the development of suitable tyrosinase inhibitor/s for the prevention of hyperpigmentation. However, a detailed in vivo study is required for glabridin derivatives to suggest these molecules as anti-melanogenic compound.
Graphical abstract
Supplementary Information
The online version contains supplementary material available at 10.1007/s13596-022-00640-8.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.