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  • Kumar et al studied Umbelliferone D galactopyranoside UFG be

    2020-02-27

    Kumar et al. studied Umbelliferone β-D-galactopyranoside (UFG) (benzopyrone), found in many plants exhibiting numerous pharmacological actions. The results of the study showed that UFG in a dose of 10, 20 or 40mgkg-1 per day, helps to prevent paw edema and arthritic score development for arthritis in rats, COX inhibition assay UFG was found to act prominently to inhibit COX-2 then COX-1, which suggests its plausible mechanism of action. The current study clearly indicates that UFG possesses anti-inflammatory effects against CFA induced arthritis via suppressing COX-2 inhibition [84].
    Synthetic coumarins A number of coumarin derivatives have been synthesized and studied through numerous synthetic, most popular being Pechmann condensation for their physical and biological properties [6], [14], [18], [22], [85]. Few groups have even reported metal complexes of coumarins and tested them for their biological properties [86], [87], [88]. Kathuria et al. reported synthesis of N-acetylamino derivatives of coumarins and quinolones and tested them for substrate specific activity against Calreticulin transacetylase (CRTAase),which is known to catalyze the transfer of acetyl group from polyphenolic acetates (PA) to certain receptor Z-YVAD-FMK (RP), thus modulating their activity. 7-N-acetylamino-4-methylcoumarin (7-AAMC, 17) was found to be the superior substrate to platelet CRTAase and emerged as the most promising antiplatelet agent both in vitro and in vivo, further it was responsible for the inhibition of cyclooxygenase-1 (Cox-1) resulting in the down regulation of thromboxane A2 (TxA2), modulation of tissue factor and the inhibition of platelet aggregation [89]. Chandak et al. reported synthesis of eighteen 2-amino-substituted 4-coumarinylthiazoles 52 bearing the benzenesulfonamide moiety. Results revealed that six compounds pronounced anti-inflammatory activity comparable to the standard drug indomethacin, further docking studies confirmed that (R1=R=Cl) was found most active with COX-1 and COX-2 active sites. In addition, substituted pyrazole nucleus into the scaffold significantly enhanced AI activity [90]. Dawood et al. reported synthesis and their anti-inflammatory activities two new series of coumarin derivatives incorporating thiazoline 53 and thiazolidinone 54 moieties. Most of the synthesized compounds demonstrated exceptionally high in vivo anti-inflammatory activity and displayed superior GI safety profiles (0–7% ulceration) as compared to indomethacin. All the showed in vitro high affinity and selectivity toward the COX-2 isoenzyme, compared to the reference celecoxib with IC50 values ranging from 0.31 to 0.78μM. Quantitative structure-activity relationship study (QSAR) was done and resulted in a highly predictive power R2 (0.908). A molecular docking study further revealed a relationship between the docking affinity and the biological results [91]. Gamal et al. reported a series of fused tricyclic coumarin sulfonate 55 derivatives and it’s in vitro antiproliferative activities against a panel of 57 human cancer cell lines of nine different cancer types were tested at the NCI. Compounds(R=Ph,p-tolyl,tert-butyl-C6H4,p-(F)C6H4, Ph[n=2]) showed the highest mean percentage of inhibition values over the 57 cell line panel at 10μM, and they were further tested in 5-dose testing mode to determine their IC50 values, further they were tested for inhibitory effect over cyclooxygenase-2 (COX-2) enzyme as a possible mechanism of action. Furthermore, in silico studies for conducted the five compounds seemed to comply with Lipinski\'s rule of five, and hence estimate their oral bioavailability [92]. Similar studies were reported by the same group, compounds [R=Me, Et, Ph, etc.; X=(CH2)n; n=1, 2]and evaluated them for their abilities to inhibit NO and PGE2 productions in LPS-induced RAW 264.7 macrophages. Compounds [R=4-F3CC6H4, X=CH2] showed the highest inhibitory effects on NO and PGE2 productions,it not only inhibited COX-2 activity but also reduced expressions of COX-2 and iNOS. Morever, ADME profiling showed that compound 55 [R=4-F3CC6H4, X=CH2] and several other compds. should be orally bioavailable [93].