Designing of a novel curcumin analogue to inhibit mitogen-activated protein kinase: A cheminformatics approach
Vakhariya Sakina S, Saurav Kumar Mishra, Kanchan Sharma, John J. Georrge · Journal of Phytonanotechnology and Pharmaceutical Sciences · 2023
Turmeric (Curcuma longa L.) is a medicinal plant used in Ayurveda, Unani and Siddha medicine as home remedies for various diseases.C. longa, botanically related to ginger (Zingiberaceae family), is a perennial plant with a short stem, large oblong leaves and bears ovate, pyriform or oblong rhizomes, which are often branched and brownish-yellow in colour.In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, antiamyloid, antioxidant, and anti-inflammatory properties.Curcumin is a highly pleiotropic molecule capable of interacting with numerous molecular targets involved in inflammation, and it modulates the inflammatory response by down-regulating the activity of cyclooxygenase-2 (COX-2), lipoxygenase, and inducible nitric oxide synthase (iNOS) enzymes; inhibits the production of the inflammatory cytokines tumour necrosis factor-alpha (TNF-a), interleukin (IL) -1, -2, -6, -8, and -12, monocyte chemoattractant protein (MCP), and migration inhibitory protein; and down-regulates mitogen-activated and Janus kinases.The derivatives of curcumin, bisdemethoxy curcumin and demethoxycurcumin also have antioxidant activity, and curcumin also reduces oxidised proteins in amyloid pathology in Alzheimer's patients.This study aims to find a novel analogue of curcumin that targets multiple pathways in the body, as curcumin is found to have low bioavailability in vivo.With the help of an advanced computational tool, the Analog molecules are constructed with database search and the SmiLib combinatorial library approach.Docking studies of analogues referenced to curcumin and its derivatives revealed few analogues that could be gained as drugs to inhibit MAPKs (ERK1).