Abstract:In this study, numerous coumarin compounds were synthesized by Pechmann and Knoevenagel methods, and the substitution of the formyl group was provided by the Duff reaction. The FTIR spectra and melting points of the synthesized compounds were compared with the literature values. The structures were also confirmed by GC/MS analysis. Besides, the synthesized coumarin derivatives were compared in terms of antioxidant activity according to DPPH and CUPRAC methods. The main aim of the study is to determine the effe… Show more
“…The key intermediate acid chloride 3 was prepared in good yield as pale-yellow crystals according to published method 21 , 46 , 47 , by the reaction of coumarin- 3 -carboxylic acid 1 and thionyl chloride (SOCl 2 ) refluxed for 2 h as depicted in Scheme 1 . Scheme 1 Synthetic pathway of coumarin-3-carbonyl chloride; synthesis of 4-bis amino quinoline 6a–e and synthesis of coumarin hybrids 7a–e .…”
Section: Resultsmentioning
confidence: 99%
“…The key intermediate acid chloride 3 was prepared in good yield as pale-yellow crystals according to published method 21,46,47 , by the reaction of coumarin-3-carboxylic acid 1 and thionyl chloride (SOCl 2 ) refluxed for 2 h as depicted in Scheme 1.…”
Section: Synthesis Of Coumarin-3-carbonyl Chloridementioning
confidence: 99%
“…The main goals of this pharmacophore merging approach consist in the interaction of the resulting molecule with dual or multiple targets, amplifying the biological activity and specificity, reducing the known side effects associated with each hybrid part, reducing the drug-drug interactions when compared with conventional classic drugs [10][11][12] . In this context, coumarin constitutes a unique motif for the construction of various classes of biologically active analogues with wide variety of pharmacological activities 13 , such as antidepressants 14 , antimicrobials [15][16][17][18] , antioxidants [19][20][21] , anti-inflammatories 20,22 , antinociceptives 23 , antitumors [24][25][26] , antiasthmatics 27 , antivirals 28 , antifungal 29 and anticoagulant activities. 30,31 Previous studies showed that the hybridization of coumarin at C-4 and C-3 positions with heterocycles have synergistic effect on biological activity.…”
A series of new coumarin-N-heterocyclic hybrids, coumarin-quinolines 7a–e, coumarin-acridines 10b,c and coumarin-neocryptolepines 13b,c were synthesized and evaluated for their anticancer and antimicrobial activities. The structures of all synthesized hybrids were confirmed by FT-IR, 1H-NMR, 13C-NMR, and MS spectrometry. The anti-proliferative activity of hybrids 7a–e, 10c and 13c were bio-evaluated using MTT-assay against colon (CaCo-2), lung (A549), breast (MDA-MB-231), and hepatocellular carcinoma (HepG-2) human cancer cell lines using doxorubicin as a reference drug. The results demonstrated that, all hybrids displayed moderate to good anti-proliferative activity against the cell lines. The most active hybrids were 7a–d and 10c against CaCo-2 cancer cell line with IC50: 57.1, 52.78, 57.29, 51.95 and 56.74 µM, and selectivity index 1.38, 1.76, 2.6, 1.96 and 0.77; respectively. While, 7a,d were potent against A549 cancer cell line with IC50: 51.72, 54.8 µM and selectivity index 1.5, 0.67; respectively. Moreover, 7c showed the most potency against MDA-MB-231 cancer cell line with IC50: 50.96 µM and selectivity index 2.20. Interestingly, docking results revealed that binding energy of the current compounds showed marked affinity values ranging from -6.54 to -5.56 kcal with interactions with the reported key amino acid SER 79. Furthermore, the antimicrobial activity of the synthesized hybrids 7a–e, 10b,c, 13b and 13c were evaluated against Gram‐positive and Gram‐negative bacterial and fungal strains. The hybrids 10b, 13b, 10c, and 13c exhibited broad-spectrum antibacterial activity against E.coli, S. mutans, and S. aureus with MIC from 3.2 to 66 µM, this hybrids also displayed antifungal activity against C. albicans with MIC values ranging from 0.0011 to 29.5 µM. In-silico investigation of the pharmacokinetic properties indicated that tested hybrids had high GI absorption, low Blood Brain Barrier (BBB) permeability in addition to cell membrane penetrability.
“…The key intermediate acid chloride 3 was prepared in good yield as pale-yellow crystals according to published method 21 , 46 , 47 , by the reaction of coumarin- 3 -carboxylic acid 1 and thionyl chloride (SOCl 2 ) refluxed for 2 h as depicted in Scheme 1 . Scheme 1 Synthetic pathway of coumarin-3-carbonyl chloride; synthesis of 4-bis amino quinoline 6a–e and synthesis of coumarin hybrids 7a–e .…”
Section: Resultsmentioning
confidence: 99%
“…The key intermediate acid chloride 3 was prepared in good yield as pale-yellow crystals according to published method 21,46,47 , by the reaction of coumarin-3-carboxylic acid 1 and thionyl chloride (SOCl 2 ) refluxed for 2 h as depicted in Scheme 1.…”
Section: Synthesis Of Coumarin-3-carbonyl Chloridementioning
confidence: 99%
“…The main goals of this pharmacophore merging approach consist in the interaction of the resulting molecule with dual or multiple targets, amplifying the biological activity and specificity, reducing the known side effects associated with each hybrid part, reducing the drug-drug interactions when compared with conventional classic drugs [10][11][12] . In this context, coumarin constitutes a unique motif for the construction of various classes of biologically active analogues with wide variety of pharmacological activities 13 , such as antidepressants 14 , antimicrobials [15][16][17][18] , antioxidants [19][20][21] , anti-inflammatories 20,22 , antinociceptives 23 , antitumors [24][25][26] , antiasthmatics 27 , antivirals 28 , antifungal 29 and anticoagulant activities. 30,31 Previous studies showed that the hybridization of coumarin at C-4 and C-3 positions with heterocycles have synergistic effect on biological activity.…”
A series of new coumarin-N-heterocyclic hybrids, coumarin-quinolines 7a–e, coumarin-acridines 10b,c and coumarin-neocryptolepines 13b,c were synthesized and evaluated for their anticancer and antimicrobial activities. The structures of all synthesized hybrids were confirmed by FT-IR, 1H-NMR, 13C-NMR, and MS spectrometry. The anti-proliferative activity of hybrids 7a–e, 10c and 13c were bio-evaluated using MTT-assay against colon (CaCo-2), lung (A549), breast (MDA-MB-231), and hepatocellular carcinoma (HepG-2) human cancer cell lines using doxorubicin as a reference drug. The results demonstrated that, all hybrids displayed moderate to good anti-proliferative activity against the cell lines. The most active hybrids were 7a–d and 10c against CaCo-2 cancer cell line with IC50: 57.1, 52.78, 57.29, 51.95 and 56.74 µM, and selectivity index 1.38, 1.76, 2.6, 1.96 and 0.77; respectively. While, 7a,d were potent against A549 cancer cell line with IC50: 51.72, 54.8 µM and selectivity index 1.5, 0.67; respectively. Moreover, 7c showed the most potency against MDA-MB-231 cancer cell line with IC50: 50.96 µM and selectivity index 2.20. Interestingly, docking results revealed that binding energy of the current compounds showed marked affinity values ranging from -6.54 to -5.56 kcal with interactions with the reported key amino acid SER 79. Furthermore, the antimicrobial activity of the synthesized hybrids 7a–e, 10b,c, 13b and 13c were evaluated against Gram‐positive and Gram‐negative bacterial and fungal strains. The hybrids 10b, 13b, 10c, and 13c exhibited broad-spectrum antibacterial activity against E.coli, S. mutans, and S. aureus with MIC from 3.2 to 66 µM, this hybrids also displayed antifungal activity against C. albicans with MIC values ranging from 0.0011 to 29.5 µM. In-silico investigation of the pharmacokinetic properties indicated that tested hybrids had high GI absorption, low Blood Brain Barrier (BBB) permeability in addition to cell membrane penetrability.
“…In addition, coumarins are a different type of biologically active organic structures having oxygen‐containing heterocycles and are used in typical human diseases such as cancer, [11] viral, [12] bacterial [13] /fungal infections, [14] tuberculosis, [15] blood coagulation, [16] and malaria [17] . These compounds also show significant biological or pharmacological activities such as antioxidant, [18] antidiabetic, [19] anti‐HIV, [20] anti‐inflammatory, [21] hepatoprotective [22] etc. Therefore, coumarin and its derivatives have also attracted much interest in synthetic organic and medicinal chemistry in the last years.…”
Methoxy group enriched eight coumarin-chalcone hybrid derivatives were synthesized. Antimicrobial/ antiproliferative activities were tested against eight human pathogenic microorganisms and four cancer cell lines (AGS, HepG2, MCF-7 and PC-3), respectively. Antimicrobial results showed that most of the compounds were almost more active than used standard antibiotics. Cytotoxicity results showed that 2,3,4-trimethoxyphenyl and thiophene containing structures have promising antiproliferative effects against AGS gastric cell lines with ~5 μg/ml IC 50 values. At the same time, 2,4-dimethoxyphenyl bearing derivative exhibited the lowest IC 50 values against HepG2 (~10 μg/ml) and PC-3 (~5 μg/ml) cell lines. Particularly, the cell viabilities of MCF-7 cell lines were remarkably inhibited by all the compounds with lower IC 50 values. Therefore, molecular docking studies between hybrid ligands and quinone reductase-2 enzyme (regulates in MCF-7 cancer cells) were performed. The results demonstrated that all the derivatives can smoothly interact with interested enzyme in agreement with the experimental results. Finally, ADME parameters were studied to reveal drug-likeness potentials of the coumarinchalcone hybrids.
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