Combination of Umbelliprenin and Arsenic Trioxide Acts as an Effective Modality Against T-Cell Leukemia/Lymphoma Cells

Adult T-cell leukemia/lymphoma (ATLL) is a serious blood malignancy with distinct geographical distribution. ATLL patients have a short survival time because of intrinsic chemoresistance and severe immunosuppression. To introduce a novel treatment, we investigated whether umbelliprenin (UMB), a natural coumarin derivative, could improve the toxicity of arsenic trioxide (ATO) on ATLL cells. To determine the viability of MT-2 cells upon treatment with different concentrations of UMB and ATO, alamarBlue assay was applied. Cell cycle analysis was carried out by propidium iodide staining and the expression of candidate genes was assessed by quantitative reverse transcription-polymerase chain reaction. Our findings revealed that combination of UMB and ATO induced considerable cytotoxic effects on ATLL cells. Flow cytometry analysis indicated accumulation of MT-2 cells in the sub G1 phase of the cell cycle after combinatorial treatment. In addition, significant downregulation in BMI-1, CD44, c-MYC, and nuclear factor-κB (REL-A) expression was observed after UMB + ATO administration. Agents with low side effects are potential candidates for novel cancer treatments. We demonstrated, for the first time, that combination of UMB and ATO might be regarded as an effective regimen for ATLL treatment.

Two Biotechnological Approaches to the Preparative Synthesis of Natural Dihydrocoumarin

In this work, we describe two different biotechnological processes that provide the natural flavour dihydrocoumarin in preparative scale. Both the presented approaches are based on the enzyme-mediated reduction of natural coumarin. The first one is a whole-cell process exploiting the reductive activity of the yeast Kluyveromyces marxianus, a Generally Recognized As Safe (GRAS) microorganism that possesses high resistance to the substrate toxicity. Differently, the second is based on the reduction of natural coumarin by nicotinamide adenine dinucleotide phosphate (NADPH) and using the Old Yellow Enzyme reductase OYE2 as catalyst. NADPH is used in catalytic amount since the co-factor regeneration is warranted employing an enzymatic system based on glucose oxidation, in turn catalysed by a further enzyme, namely glucose dehydrogenase (GDH). Both processes compare favourably over the previously reported industrial method as they work with higher coumarin concentration (up to 3 g/L for the enzymatic process) yet allowing the complete conversion of the substrate. Furthermore, the two approaches have significant differences. The microbial reduction is experimentally simple but the isolated dihydrocoumarin yield does not exceed 60%. On the contrary, the enzymatic approach requires the use of two specially prepared recombinant enzymes, however, it is more efficient, affording the product in 90% of isolated yield.

Comparative Antiseizure Analysis of Diverse Natural Coumarin Derivatives in Zebrafish

Coumarins are a well-known group of plant secondary metabolites with various pharmacological activities, including antiseizure activity. In the search for new antiseizure drugs (ASDs) to treat epilepsy, it is yet unclear which types of coumarins are particularly interesting as a systematic analysis has not been reported. The current study performed behavioral antiseizure activity screening of 18 different coumarin derivatives in the larval zebrafish pentylenetetrazole (PTZ) model using locomotor measurements. Activity was confirmed for seven compounds, which lowered seizure-like behavior as follows: oxypeucedanin 38%, oxypeucedanin hydrate 74%, notopterol 54%, nodakenetin 29%, hyuganin C 35%, daphnoretin 65%, and pimpinellin 60%. These coumarins, together with nodakenin, underwent further antiepileptiform analysis by local field potential recordings from the zebrafish opticum tectum (midbrain). All of them, except for nodakenetin, showed pronounced antiepileptiform activity, decreasing PTZ-induced elevation in power spectral density (PSD) by 83–89% for oxypeucedanin, oxypeucedanin hydrate, and notopterol, 77% for nodakenin, 26% for nodakenetin, 65% for hyuganin C, 88% for daphnoretin, and 81% for pimpinellin. These data demonstrate the potential of diverse coumarin scaffolds for ASD discovery. Finally, the structural differences between active and inactive coumarins were investigated in silico for oxypeucedanin hydrate and byacangelicin for their interaction with GABA-transaminase, a hypothetical target.

A review on Coumarin derivatives as potent anti-Tuberculosis agent

Background: : Tuberculosis (TB) is an acute or chronic infectious disease caused by several species of Myco-bacterium, collectively called as tubercle bacilli or Mycobacterium tuberculosis complex. Around 10 million people get sick with tuberculosis (TB) each year. TB is the second leading cause of deaths today after HIV/AIDS. A serious problem in the context of MDR-TB, is the extensively drug-resistant TB which is an im-portant reason for the restricted chemotherapy in TB. Therefore, there is a need to explore new antitubercular (anti-TB) agents. Coumarin is an oxygen-containing heterocyclic compound and can be widely found in many natural products, and many of them display diverse biological activities.The wide spectrum of activities of coumarin molecules have intrigued the scientists to explore the natural coumarins and their synthetic deriva-tives for their potential as anti-TB drugs. Objective: The objective of this review is to emphasize on important coumarin analogs with anti-TB activities and their structure-activity relationships (SAR) for designing better anti-TB agents. Method: Latest, authentic and published reports on various synthetic and natural coumarin derivatives and their anti-TB activities is being thoroughly studied and analyzed. The structural requirements of coumarins as anti-TB drugs have also been studied. Results : Collection and compilation of reports on various synthetic and natural coumarin derivatives and their anti-TB activities is being done. Conclusion: The study provides latest report on coumarin derivatives synthesized as anti-TB agent and wheth-er their activity depends on structural changes or not.

Medicinal Research Progress of Natural Coumarin and its Derivatives

Abstract:: Coumarins- a natural class of compounds, firstly isolated from Tonka beans and are found in various medicinal herbs. This class of compounds has been reported of remarkable biological and pharmacological applications including antimicrobial, anticoagulants, anti-inflammatory as well as cancer. Additionally, coumarins have revealed significant inhibition of different human cancers viz bladder cancer, lung cancer, prostate cancer, ovarian cancer, colon cancer, breast cancer, gastric cancer, leukemia, pancreatic cancer and still counting. Therefore, the compilation of medicinal research progress of natural coumarin and its derivatives will be beneficial for scientists and researchers worldwide. The literature review of medicinal research progress of natural coumarin and its derivatives was collected from various databases including PubMed, Web of Science and Science Direct from the year 1942 to date.The presented data on medicinal research progress of natural coumarin and its derivatives provides a detailed review which could serve as a platform for future research.The data presented the medicinal and biological activities of coumarin and its derivatives like antimicrobial, anticoagulant, anti-inflammatory and anticancer in particular. This could be utilized for future formulation and development of drugs and references based on coumarin and its derivatives.