Anticancer Properties and Clinical Trials of Coumarins: A Review (original) (raw)
Related papers
European Journal of Medicinal Chemistry, 2015
Coumarins are fused benzene and pyrone ring systems which prompt biological investigation to assess their potential therapeutic significance. It possesses immeasurable anticancer potential with minimum side effects depending on the substitutions on the basic nucleus. Coumarins have a tremendous ability to regulate diverse range of cellular pathways that can be explored for selective anticancer activity. This is the first standalone review that emphasis on the assorted retrosynthetic approaches, important targets for molecularly targeted cancer therapy and structure activity relationship studies that highlight the chemical groups responsible for evoking the anticancer potential of coumarin derivatives reported from 2011 to 2014.
Cytotoxic and Antitumor Activity of some Coumarin Derivatives
Natural Product Communications
Several natural and synthetic coumarins were assayed against different cancer cell lines. Four of them have shown cytotoxicity against a panel of three human solid tumor cell lines (HeLa, T-47D, and WiDr) and a clearly activity/hydrophobicity relationship. Compound 13 proved to be the most active product in all cell lines tested, with values of 8.0 (±0.38) μM against HeLa cells and also able to inhibit Taq DNA polymerase. This dual activity of 13 makes it a candidate to be considered as a “lead” compound in the search for novel antitumor drugs.
Antioxidant, Anticancer and Immunocytochemistry Activities of Three Synthetic Coumarin Derivatives
Fayoum Journal of Agricultural Research and Development, 2017
Many biological studies have indicated that coumarin and its derivatives can act as chemoperventive agents. In this study, three synthetic coumarin derivatives were investigated for their free radical scavenging, anticancer and cell signaling activities. Compound A showed antioxidant effects with 100% decoloration of DPPH at concentration of more than 150 µg/ml with IC 50 of 102.12 ± 0.15 µg/ml. Compound B and C induced antioxidant effects with 100% decoloration at 100 and 50 µg/ml, respectively. Also, the IC 50 of compounds B and C was 28.35 ± 0.04 and 6.12 ± 0.05 µg/ml, respectively. Moreover, these compounds suppressed PC-3 prostate and MDA-MB-453 breast cancer cells proliferation with IC 50 of 20 µM, 70 µM and 50 µM, respectively for PC-3 cells. However, it needs higher dosage to inhibit MDA-MB-453 breast cancer cell growth with IC 50 at 25 µM, 137 µM and 100 µM, respectively. All of these compounds activated the apoptotic death signals downstream by activating caspase pathway. And showed many apoptotic characterizations including, DNA fragmentation and apoptotic bodies formation.
Synthesis and Evaluation of New Coumarins as Antitumor and Antioxidant Applicants
Journal of Medicinal and Chemical Sciences, 2022
This work involves the synthesis of eight novel fused coumarin compounds, which were confirmed by various spectrophotometers and then, assessed for their apoptotic-inducing and free radical-quenching activities. The pharmacokinetic parameters were evaluated in silico using pre-ADMET, a free online program. The apoptotic-inducing activity was tested against six tumorigenic cell lines. Also, their safety against normal cells was examined. The free radical-quenching activity was assessed by checking these compounds' ability to eliminate DDPT and hydroxyl moieties. Pharmacokinetic investigations showed that the synthesized fused coumarin compounds have excellent penetration across the GIT mucosa and most of them have poor penetration across the blood-brain barrier. These findings suggest good oral bioavailability along with low neurological toxicity profiles. The evaluation of the apoptotic-inducing activity revealed that all of the compounds have weaker activity as compared to the reference. Among these compounds, SA4 was the most potent one. Nevertheless, all of these new compounds had an excellent safety profile against normal cells. On the other hand, the assessment of the free radical-quenching activity of these synthesized compounds also indicated that all of them were less active than the reference. In this field, SA0 was the strongest free radical-quenching compound. From these realizations, along with the apparent safety and good pharmacokinetic characteristics in accordance with the in silico study, compounds SA4 and SA0 are considered the most promising agents. The authors hope that these new fused coumarin compounds can be utilized in the coming years for the production of new powerful drugs with apoptoticinducing and free radical-quenching potentials which can help in the battle against many diseases.
Journal of Heterocyclic Chemistry, 2018
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-3carbonitrile attached to C 6 position, fused pyrazolone ring or attached to 4-chlorophenyl-2-oxodihydropyridine-3-carbonitrile at C 3 position of the coumarin nucleus, respectively, exhibited moderate to strong activity against both cell lines.
A twenty-year journey exploring coumarin-based derivatives as bioactive molecules
Frontiers in Chemistry, 2022
The coumarin core (i.e., 1-benzopyran-2 (2H)-one) is a structural motif highly recurrent in both natural products and bioactive molecules. Indeed, depending on the substituents and branching positions around the byciclic core, coumarin-containing compounds have shown diverse pharmacological activities, ranging from anticoagulant activities to anti-inflammatory, antimicrobial, anti-HIV and antitumor effects. In this survey, we have reported the main scientific results of the 20-years investigation on the coumarin core, exploited by the research group headed by Prof. Angelo Carotti (Bari, Italy) either as a scaffold or a pharmacophore moiety in designing novel biologically active small molecules.
Current pharmaceutical design, 2004
The Benzopyrones are a group of compounds whose members include coumarins and flavonoids. Dietary exposure to benzopyrones is quite significant, as these compounds are found in vegetables, fruit, seeds, nuts, coffee, tea and wine. It is estimated that the average western diet contains approximately 1g/day of mixed benzopyrones. It is, therefore, not difficult to see why extensive research into their pharmacological and therapeutic properties is underway over many years. Coumarin is a natural substance that has shown anti-tumour activity in vivo, with the effect believed to be due to its metabolites (e.g. 7-hydroxycoumarin). This review is based on recent studies of coumarins and coumarin related compounds. Therefore, the focus will be on these relevant compounds and their therapeutic importance. A recent study has shown that 7-hydroxycoumarin inhibits the release of Cyclin D1, which is overexpressed in many types of cancer. This knowledge may lead to its use in cancer therapy. Esculetin inhibits growth and cell cycle progression by inducing arrest of the G 1 phase in HL-60 leukaemia cells, resulting from the inhibition of retinoblastoma protein phosphorylation. Recent studies investigating the potential of flavonoids as therapeutic agents have suggested they may have use in various therapeutic settings ranging from leukaemia treatment to the treatment of patients with HIV. Genistein is a well-known isoflavone and is a tyrosine kinase inhibitor. Studies have indicated that genistein elicits inhibitory effects on cell growth of various carcinoma cell-lines and may be a potential candidate for cancer therapy. In our research, we have investigated the effects of coumarins and coumarin-related compounds on a panel of cell-lines. The most recent work involves two cell-lines, MCF-7 a breast carcinoma and A549 a lung carcinoma. Microtitre assays were performed along with real-time analysis of cell viability using a biosensor called the Cytosensor microphysiometer. These studies suggest that both genistein and esculetin exerted the most potent inhibitory effect on cell growth in comparison to the other two compounds.
Synthesis and Pharmacological Evaluation of Novel Coumarin Derivatives
International Journal of Research in Pharmaceutical Sciences, 2020
The current work focuses on new architecture, synthesis of coumarinoxadiazole hybrid derivative products as both these (coumarin ring and oxadiazole) have a wide variety of biological behavior, Compounds containing the nucleus of coumarin (2H-1-benzopyran-2-one) are an interesting class of hetero cycles which hold an important role in the ield of natural ingredients and synthetic organic chemistry. It has been exciting medicinal chemists to study native coumarins or synthetic analogs for their application for decades. And they can be further modi ied to synthesize more effective and potent drugs. Compounds have been characterized by spectrophotometry of physicochemical properties and their structures veri ied by infrared spectroscopy (FTIR) and nuclear magnetic resonance (1H-NMR) Such new derivatives of coumarinyl-oxadiazole was quali ied to estimate the lethal dose, anticancer, anticoagulant and antioxidant activity. Their pharmacological properties depend on their pattern of substitution, compound S4F proved signi icant anticoagulant activity in concentration (50, 100, 200 mg/ml) similar for heparin, and monitor the coagulation effect on plasma, while compound S 4 CO give signi icant anticancer activity against MCF-7 a breast cancer cell. Speci ic compounds have strong antioxidants with the effective action of radical scavengers; the S4Cl compound with IC50 1.49 is the most potent antioxidant activity note. Basically, all the formulations tested reported satisfactory behavior. The review shows that varieties of coumarin derivatives have synthesized and shown anti-cancer, antioxidant and anti-coagulant potentials. These derivatives synthesis and its biological assay can be further modi ied in the future to improve the anti-cancer, anti-oxidant and anticoagulant potentials of the versatile coumarin nucleus.
European journal of medicinal chemistry, 2017
A small library of coumarins, carrying butynyl-amino chains, was synthesized continuing our studies in the field of MDR reverting ageEnts and in order to obtain multipotent agents to combat malignancies. In particular, the reported anticancer and chemopreventive natural product 7-isopentenyloxycoumarin was linked to different terminal amines, selected on the basis of our previously reported results. The anticancer behaviour and the MDR reverting ability of the new compounds were evaluated on human colon cancer cells, particularly prone to develop the MDR phenotype. Some of the new derivatives showed promising effects, directly acting as cytotoxic compounds and/or counteracting MDR phenomenon. Compound 1e emerged as the most interesting of this series, showing a multipotent biological profile and suggesting that conjugation of an appropriate coumarin core with a properly selected butynyl-amino chain allows to obtain novel hybrid molecules endowed with improved in vitro antitumor acti...