Novel Coumarin Derivatives Containing 1,2,4-Triazole, 4,5-Dicyanoimidazole and Purine Moieties: Synthesis and Evaluation of Their Cytostatic Activity

Benci, Krešimir; Mandić, Leo; Suhina, Tomislav; Sedić, Mirela; Klobučar, Marko; Pavelić, Sandra Kraljević; Pavelić, Krešimir; Wittine, Karlo; Mintas, Mladen

doi:10.3390/molecules170911010

Cited by 47 publications

(26 citation statements)

References 32 publications

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“…Natural products are inexhaustible as a source of chemical structures and for more than a century have been used as scaffolds for the synthesis of new drugs. The coumarins, phenolic compounds which possess a benzopyranone nucleus [4] are one of the major classes of secondary metabolites, which has been highlighted in biological studies as being (anti-HIV [5], hepato-protective [6], anti-inflammatory [7], antimicrobial [8], antimitotic [9] and antitumor [10]), and in part, due to their antifungal properties [11–13] they are believed to exert a role in plant protection against herbivorous, fungal, and bacterial infections [14]. …”

Section: Introductionmentioning

confidence: 99%

Synthesis, Structure-Activity Relationships (SAR) and in Silico Studies of Coumarin Derivatives with Antifungal Activity

Araújo

Guerra

Lima

et al. 2013

IJMS

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The increased incidence of opportunistic fungal infections, associated with greater resistance to the antifungal drugs currently in use has highlighted the need for new solutions. In this study twenty four coumarin derivatives were screened in vitro for antifungal activity against strains of Aspergillus. Some of the compounds exhibited significant antifungal activity with MICs values ranging between 16 and 32 μg/mL. The structure-activity relationships (SAR) study demonstrated that O-substitutions are essential for antifungal activity. It also showed that the presence of a short aliphatic chain and/or electron withdrawing groups (NO2 and/or acetate) favor activity. These findings were confirmed using density functional theory (DFT), when calculating the LUMO density. In Principal Component Analysis (PCA), two significant principal components (PCs) explained more than 60% of the total variance. The best Partial Least Squares Regression (PLS) model showed an r2 of 0.86 and q2cv of 0.64 corroborating the SAR observations as well as demonstrating a greater probe N1 interaction for active compounds. Descriptors generated by TIP correlogram demonstrated the importance of the molecular shape for antifungal activity.

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Section: Introductionmentioning

confidence: 99%

Synthesis, Structure-Activity Relationships (SAR) and in Silico Studies of Coumarin Derivatives with Antifungal Activity

Araújo

Guerra

Lima

et al. 2013

IJMS

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“…Some of these agents are in different phases of clinical trials, and it may be expected that the number will increase in the future. Coumarins, a group of dietary phytochemicals, have recently attracted much attention because of their broad spectrum of pharmacological activities, including anticancer activity [3,23,31]. 3, 9-dihydroxy-2-prenylcoumestan (psoralidin, pso), a furanocoumarin, is one of the major furanocoumarins isolated from the traditional Asian medicinal plant Psoralea corylifolia .…”

Section: Introductionmentioning

confidence: 99%

Molecular interplay between cdk4 and p21 dictates G0/G1 cell cycle arrest in prostate cancer cells

et al. 2013

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This study examined the effect of 3, 9-dihydroxy-2-prenylcoumestan (pso), a furanocoumarin, on PC-3 and C4-2B castration-resistant prostate cancer (CRPC) cell lines. Pso caused significant G0/G1 cell cycle arrest and inhibition of cell growth. Molecular analysis of cyclin (D1, D2, D3, and E), cyclin-dependent kinase (cdk) (cdks 2, 4, and 6), and cdk inhibitor (p21 and p27) expression suggested transcriptional regulation of the cdk inhibitors and more significant downregulation of cdk4 than of cyclins or other cdks. Overexpression of cdk4, or silencing of p21 or p27, overcame pso-induced G0/G1 arrest, suggesting that G0/G1 cell cycle arrest is a potential mechanism of growth inhibition in CRPC cells.

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“…Anticancer [1][2][3], antibacterial [4], antiviral [5], anti-inflammatory [6], anticoagulant [7], acetyl, and butyryl cholinesterase inhibitory activity [8,9] are widely reported biological activities of various coumarin derivatives. Anticancer [1][2][3], antibacterial [4], antiviral [5], anti-inflammatory [6], anticoagulant [7], acetyl, and butyryl cholinesterase inhibitory activity [8,9] are widely reported biological activities of various coumarin derivatives.…”

Section: Introductionmentioning

confidence: 99%

Facile Synthesis and Anticancer Activity Study of Novel Series of Substituted and Fused Coumarin Derivatives

Hassan

Sarg

Deeb

et al. 2018

Journal of Heterocyclic Chem

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Various new substituted and fused coumarin analogues have been synthesized via different synthetic pathways. Among which are variable substituted coumarin derivatives bearing either biologically active side chains or rings at 5, 6, and 3 positions of the coumarin nucleus as indicated in compounds 10, 12, 13, 16–19, 21, 23–32, 38, and 42–45. In addition, different pyranocoumarin derivatives either substituted as in compounds 2, 3, and 6 or fused as compounds 33–36, pyranoxanthene analogues such as compounds 4 and 46, coumarinotriazolothiadiazine derivative 8, coumarinonaphthodiazocin analogue 39 and coumarinopyrazolone derivative 40 were synthesized. Thirty‐eight of the synthesized compounds were subjected to in vitro anticancer screening against mammalian liver carcinoma HepG2 and breast carcinoma MCF7 cell lines using Cisplatin as a standard reference. The anticancer activity screening results revealed that, among the tested compounds, compounds 16, 40, and 43 bearing 4‐chlorophenyl‐2‐aminopyridine‐3‐carbonitrile attached to C6 position, fused pyrazolone ring or attached to 4‐chlorophenyl‐2‐oxo‐dihydropyridine‐3‐carbonitrile at C3 position of the coumarin nucleus, respectively, exhibited moderate to strong activity against both cell lines.

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Novel Coumarin Derivatives Containing 1,2,4-Triazole, 4,5-Dicyanoimidazole and Purine Moieties: Synthesis and Evaluation of Their Cytostatic Activity

Cited by 47 publications

References 32 publications

Synthesis, Structure-Activity Relationships (SAR) and in Silico Studies of Coumarin Derivatives with Antifungal Activity

Synthesis, Structure-Activity Relationships (SAR) and in Silico Studies of Coumarin Derivatives with Antifungal Activity

Molecular interplay between cdk4 and p21 dictates G0/G1 cell cycle arrest in prostate cancer cells

Facile Synthesis and Anticancer Activity Study of Novel Series of Substituted and Fused Coumarin Derivatives

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