Synthesis of Sydnone Substituted Biginelli Derivatives as Hyaluronidase Inhibitors

Abstract

A novel series of Biginelli 2-3 (a and b) and Biginelli-like compounds 4-7 (a and b) were synthesized from 3-aryl-4-formylsydnone 1 (a and b). Since the crystal structure of hyaluronidase was unavailable, the human hyaluronidase protein structure was used as template and homology modeling was performed, validated by Ramachandran plots and subjected to docking studies along with in vitro anti-inflammatory activity assessment against hyaluronidase. Compounds 2-3 (a and b) exhibited potent enzyme inhibition.

A mini-review on Biginelli adducts with notable pharmacological properties

“…5 ) was able to inhibit the activity of hyaluronidase (3–5 units) in the range from 89% to 100%. Similar results were achieved when compounds 56 – 59 were substituted for indomethacin, a reference drug [24] .…”

“…The anti-inflammatory potential of a certain molecule can be investigated by various means, such as the analgesic effect using paw edema as model, the inhibition of proinflammatory cytokines (e.g. tumor necrosis factor (TNF-α) and interleukin 6 (IL-6)) [20] , the effect on prostaglandin E 2 and/or hialuronidase, nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and transient receptor A1 (TRPA1), among others [20–24] .…”

“…Chronic inflammation is known to be associated with increased activity of hyaluronidases, enzymes that catalyzes the degradation of hyaluronic acid [27,28] . Based on this, Gireesh and coworkers performed molecular docking studies using some Biginelli adducts and related derivatives to identify compounds with potential to inhibit hyaluronidase [24] . Indeed, in vitro assays confirmed that 100 μg of compounds 56 – 59 ( Fig.…”

One-pot synthesis, X-ray crystal structure, and identification of potential molecules against COVID-19 main protease through structure-guided modeling and simulation approach

“…The following are selective molecules having significant activity, and they are examined with clinically used drugs in vivo / in vitro, establishing QSAR ( Ashok et al, 2007 , Chiang et al, 2009 , Chitra et al, 2010 , Deshmukh et al, 2009 , Kidwai et al, 2005 , Rajanarendar et al, 2010 ). There are several reasons that Biginelli's reaction has been studied in recent decades ( Bais et al, 2020 , de Fátima et al, 2015 , Gireesh et al, 2013 , Ismaili et al, 2008 , Kaur et al, 2017 , Li et al, 2020 , Liu et al, 2019 , Mokale et al, 2010 , Rani et al, 2016 , Sawant and Sarode, 2011 , Silva et al, 2015 ).…”

Biginelli Reaction Mediated Synthesis of Antimicrobial Pyrimidine Derivatives and Their Therapeutic Properties

“…Both reactions proved to be “key methods” for the synthesis of pyridine and pyrimidine derivatives, respectively, which were greatly developed in the following period, especially due to the applications of the synthesized compounds. The Biginelli reaction has been intensively studied in the last two decades, especially due to the applications of synthesized dihydropyrimidinone compounds at the beginning, especially as calcium channel blockers of the nifedipine-type [ 4 ], and then as antitumor [ 5 , 6 , 7 , 8 ], antibacterial, antiviral [ 9 , 10 ], anti-inflammatory [ 11 , 12 ], analgesic [ 13 ], anti-Alzheimer [ 14 ], or antioxidant [ 15 ] compounds.…”