TY - JOUR
T1 - Chemistry, biosynthesis, physicochemical and biological properties of rubiadin
T2 - A promising natural anthraquinone for new drug discovery and development
AU - Watroly, Mohd Nasarudin
AU - Sekar, Mahendran
AU - Fuloria, Shivkanya
AU - Gan, Siew Hua
AU - Jeyabalan, Srikanth
AU - Wu, Yuan Seng
AU - Subramaniyan, Vetriselvan
AU - Sathasivam, Kathiresan V
AU - Ravi, Subban
AU - Rani, Nur Najihah Izzati Mat
AU - Lum, Pei Teng
AU - Vaijanathappa, Jaishree
AU - Meenakshi, Dhanalekshmi Unnikrishnan
AU - Mani, Shankar
AU - Fuloria, Neeraj Kumar
N1 - Funding Information:
The authors acknowledge AIMST University, Kedah, Malaysia, and Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, Malaysia, for providing the facilities and services required to complete the study. The figures and graphical abstract in this manuscript were created with BioRender.com and the support of https:// biorender.com under a paid subscription.
Publisher Copyright:
© 2021 Watroly et al.
PY - 2021
Y1 - 2021
N2 - Anthraquinones (AQs) are found in a variety of consumer products, including foods, nutritional supplements, drugs, and traditional medicines, and have a wide range of pharmacological actions. Rubiadin, a 1,3-dihydroxy-2-methyl anthraquinone, primarily originates from Rubia cordifolia Linn (Rubiaceae). It was first discovered in 1981 and has been reported for many biological activities. However, no review has been reported so far to create awareness about this molecule and its role in future drug discovery. Therefore, the present review aimed to provide comprehensive evidence of Rubiadin’s phytochemistry, biosynthesis, physicochemical properties, biological properties and therapeutic potential. Relevant literature was gathered from numerous scientific databases including PubMed, ScienceDirect, Scopus and Google Scholar between 1981 and up-to-date. The distribution of Rubiadin in numerous medicinal plants, as well as its method of isolation, synthesis, characterisation, physiochemical properties and possible biosynthesis pathways, was extensively covered in this review. Following a rigorous screening and tabulating, a thorough description of Rubiadin’s biological properties was gathered, which were based on scientific evidences. Rubiadin fits all five of Lipinski’s rule for drug-likeness properties. Then, the in depth physiochemical characteristics of Rubiadin were investigated. The simple technique for Rubiadin’s isolation from R. cordifolia and the procedure of synthesis was described. Rubiadin is also biosynthesized via the polyketide and chorismate/o-succinylbenzoic acid pathways. Rubiadin is a powerful molecule with anticancer, antiosteoporotic, hepatoprotective, neuroprotective, anti-inflammatory, antidiabetic, antioxidant, antibacterial, antimalarial, antifungal, and antiviral properties. The mechanism of action for the majority of the pharmacological actions reported, however, is unknown. In addition to this review, an in silico molecular docking study was performed against proteins with PDB IDs: 3AOX, 6OLX, 6OSP, and 6SDC to support the anticancer properties of Rubiadin. The toxicity profile, pharmacokinetics and possible structural modifications were also described. Rubiadin was also proven to have the highest binding affinity to the targeted proteins in an in silico study; thus, we believe it may be a potential anticancer molecule. In order to present Rubiadin as a novel candidate for future therapeutic development, advanced studies on preclinical, clinical trials, bioavailability, permeability and administration of safe doses are necessary.
AB - Anthraquinones (AQs) are found in a variety of consumer products, including foods, nutritional supplements, drugs, and traditional medicines, and have a wide range of pharmacological actions. Rubiadin, a 1,3-dihydroxy-2-methyl anthraquinone, primarily originates from Rubia cordifolia Linn (Rubiaceae). It was first discovered in 1981 and has been reported for many biological activities. However, no review has been reported so far to create awareness about this molecule and its role in future drug discovery. Therefore, the present review aimed to provide comprehensive evidence of Rubiadin’s phytochemistry, biosynthesis, physicochemical properties, biological properties and therapeutic potential. Relevant literature was gathered from numerous scientific databases including PubMed, ScienceDirect, Scopus and Google Scholar between 1981 and up-to-date. The distribution of Rubiadin in numerous medicinal plants, as well as its method of isolation, synthesis, characterisation, physiochemical properties and possible biosynthesis pathways, was extensively covered in this review. Following a rigorous screening and tabulating, a thorough description of Rubiadin’s biological properties was gathered, which were based on scientific evidences. Rubiadin fits all five of Lipinski’s rule for drug-likeness properties. Then, the in depth physiochemical characteristics of Rubiadin were investigated. The simple technique for Rubiadin’s isolation from R. cordifolia and the procedure of synthesis was described. Rubiadin is also biosynthesized via the polyketide and chorismate/o-succinylbenzoic acid pathways. Rubiadin is a powerful molecule with anticancer, antiosteoporotic, hepatoprotective, neuroprotective, anti-inflammatory, antidiabetic, antioxidant, antibacterial, antimalarial, antifungal, and antiviral properties. The mechanism of action for the majority of the pharmacological actions reported, however, is unknown. In addition to this review, an in silico molecular docking study was performed against proteins with PDB IDs: 3AOX, 6OLX, 6OSP, and 6SDC to support the anticancer properties of Rubiadin. The toxicity profile, pharmacokinetics and possible structural modifications were also described. Rubiadin was also proven to have the highest binding affinity to the targeted proteins in an in silico study; thus, we believe it may be a potential anticancer molecule. In order to present Rubiadin as a novel candidate for future therapeutic development, advanced studies on preclinical, clinical trials, bioavailability, permeability and administration of safe doses are necessary.
KW - Anticancer
KW - Biosynthesis
KW - Pharmacology
KW - Physicochemical properties
KW - Rubia cordifolia
KW - Rubiadin
UR - http://www.scopus.com/inward/record.url?scp=85118884936&partnerID=8YFLogxK
U2 - 10.2147/DDDT.S338548
DO - 10.2147/DDDT.S338548
M3 - Review Article
C2 - 34764636
AN - SCOPUS:85118884936
VL - 15
SP - 4527
EP - 4549
JO - Drug Design, Development and Therapy
JF - Drug Design, Development and Therapy
SN - 1177-8881
ER -