<figure><img src="image_1.png" /></figure>

HAL
open science

# Cytotoxicity and antioxidant potential of dichloromethane and ethyl acetate extracts of Morinda morindoïdes leaves

Aya Honorine Tanoh, Kouassi Elisée Kporou, Anaïs Brion, Cendrine Seguin, Antoine Kichler, Benoit Frisch, Sylvie Fournel

<figure><img src="image_2.png" /></figure>

## ► To cite this version:

Aya Honorine Tanoh, Kouassi Elisée Kporou, Anaïs Brion, Cendrine Seguin, Antoine Kichler, et al.. Cytotoxicity and antioxidant potential of dichloromethane and ethyl acetate extracts of Morinda morindoïdes leaves. Journal of Drug Delivery and Therapeutics, 2024, 14 (6), pp.98 - 104. 10.22270/jddt.v14i6.6571 . hal-04737123

HAL Id: hal-04737123

https://hal.science/hal-04737123v1

Submitted on 15 Oct 2024

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

Public Domain
<figure><img src="image_3.png" /></figure>

<figure><img src="image_4.png" /></figure>

Open Access Full Text Article

<figure><img src="image_5.png" /></figure>

<figure><img src="image_6.png" /></figure>

Check for updates

Research Article

# Cytotoxicity and antioxidant potential of dichloromethane and ethyl acetate extracts of Morinda morindoïdes leaves

TANOH Aya Honorine <fnref n="1" />*, KPOROU Kouassi Elisée <fnref n="1" />, BRION Anaïs <fnref n="2" />, SEGUIN Cendrine <fnref n="2" />, KITCHLER Antoine <fnref n="2" />, FRISCH Benoit <fnref n="2" />, FOURNEL Sylvie <fnref n="2" />

## Article Info:

<figure><img src="image_7.png" /></figure>

## Article History:

Received 02 April 2024
Reviewed 04 May 2024
Accepted 26 May 2024
Published 15 June 2024

## Cite this article as:

Tanoh AH, Kporou KE, Brion A, Seguin C, Kitchler A, Frisch B, Fournel S. Cytotoxicity and antioxidant potential of dichloromethane and ethyl acetate extracts of Morinda morindoides leaves, Journal of Drug Delivery and Therapeutics. 2024; 14(6):98-104

DOI: http://dx.doi.org/10.22270/jddt.v14i6.6571

## *Address for Correspondence:

TANOH Aya Honorine, Excellence Group of Research on Products of Traditional Pharmacopoeia (GeRProPhaT, Daloa Côte D'Ivoire), Agrovalorization Laboratory, Jean Lorougnon Guede University, BP 150 Daloa, Côte d'Ivoire

## Abstract

The incidence of cancer and related mortality are on the rise worldwide, and this requires the search for new plant-based medicines. In this study, the antioxidant potential and cytotoxic activity against HCT-116 cell line were evaluated. Dichloromethane and ethyl acetate extracts of *M. morindoides* were prepared by maceration and evaluated for some biological properties. Cytotoxicity was assessed according to MTS method on the cancer line HCT-116 (colorectal carcinoma) using doxorubicin as reference. Antioxidant potential was carried out by DPPH and ABTS tests. Tri-phytochemistry was carried out from coloring and precipitation tests. On HCT-116 cell line, extracts demonstrated dose-response activity. The lowest IC50 value was obtained with the acetate extract with an IC50= 16.38 ± 0.2 µg/mL. IC50 values for antioxidant activities were evaluated at 39.70 ± 1.7 µg/mL and at 57.65 ± 4.3µg/mL by DPPH and ABTS test respectilly. Finally, phytochemical screening showed presence of polyphenols, flavonoids and quinone. *M. morindoides* ethyl acetate extract showed the best cytotoxicity and antioxidant activities. Therefore, it should be an interesting source for discovery of new compounds for colorectal cancer treatment.

**Keywords:** cytotoxicity, cancer cells, antioxidant, *Morinda morindoides*.

## INTRODUCTION

Colorectal cancer is the second leading cause of cancer-related deaths worldwide. In 2018, colorectal cancer was one of the most diagnosed cancers in the world, with 1.8 million cases and 881,000 deaths<fnref n="1" />. The number of cases is estimated to reach 20 million by 2022 <fnref n="2" />. This pathology is characterized by an anarchic proliferation of abnormal cells resulting from persistent and unrepaired DNA damage³. Risk factors that may be associated with this pathology include a diet low in fiber and high in fat, age, lifestyle, family history, and carcinogens such as ionizing radiation or ultraviolet radiation. Activated oxygen species (AOS), which include free radicals and singlet oxygen, play an important role in altering the genetic material of cells with metastatic phase in the cancer process⁴.

Treatment for colorectal cancer includes chemotherapy and radiation therapy. However, these treatment options are complex and associated with side effects that are sometimes intolerable for the patient <fnref n="1" />. In light of the above, it is necessary to search new anticancer compounds of plant origin that have minimal toxicity to normal cells and can also

neutralize oxidative stress. One of these approaches is to explore products derived from plants, which are perceived as natural products with less risk or hazard to humans and environment compared to synthetic products⁵.

*Morinda morindoides*, a climbing vine of the Rubiaceae family with opposite leaves and bumpy fruits⁶ is widely used in traditional medicine to treat certain pathologies. In Congo, the leaves are used in decoction to treat malaria, rheumatic pain⁷ and hemorrhoids⁸. The fruits are used locally to treat epilepsy. In Côte d'Ivoire, ZIHIRI *et al.* (2005), showed in their work that the ethanolic extract of this species had *in vitro* antiplasmodial activity on chloroquine-resistant FcB1/Colombia strains of *Plasmodium falciparum*⁵ the ethanolic extract of the leaves of this plant also showed good anti-vibrio cholera activity in a study conducted by Koffi (2013). With the overall objective of valorizing natural substances, the present work aims to evaluate the cytotoxic and antioxidant potential of *Morinda morindoides* leaves. Subsequently, the chemical compounds present in the extract will be determined.

<footnote n="1">¹ Excellence Group of Research on Products of Traditional Pharmacopoeia (GeRProPhaT, Daloa Côte D'Ivoire), Agrovalorization Laboratory, Jean Lorougnon Guede University, BP 150 Daloa, Côte d'Ivoire</footnote>

<footnote n="2">² Laboratoire de Conception et Application de Molécules Bioactives- Equipe 3bio Bureau F320, UMR 7199 CNRS-Université de Strasbourg, Faculté de Pharmacie, 74 Route du Rhin- BP 60024- 67401 Illkirch Cédex- France</footnote>
The lowest IC50 values indicate greater antioxidant activity of the tested product.

## Qualitative characterization of secondary metabolites

This study will highlight the main chemical groups of pharmacological interest (alkaloids, phenolic compounds, terpenes). It will be done using qualitative methods as described by¹² and based on specific chemical reactions.

### Testing for presence of alkaloids

The alkaloids were revealed using DRAGENDORFF reagents (potassium iodo-bismuthate reagent) and Valser-Mayer reagents. A volume of 6 mL of each solution was evaporated in a capsule. The residue was taken up in 6 mL of ethanol (60°). The resulting solution was divided into two test tubes. In the first tube, two drops of DRAGENDORFF were added, the appearance of a precipitate or an orange color indicates the presence of alkaloids. In the second tube, two drops of Valser-Mayer reagent were added, the appearance of a milky white precipitate indicates a positive reaction.

### Testing for presence of polyphenols

One drop of a 2% alcoholic solution of ferric chloride was added to a volume of 2 mL of extracts. Ferric chloride, in the presence of polyphenolic derivatives, gives the appearance of a more or less dark blue-blackish or green color.

### Testing for presence of flavonoids

A volume of 2 mL of each extract was evaporated to dryness in a capsule in a water bath. After cooling, the residue was taken up in five milliliters of half-dilute hydrochloric alcohol. The resulting solution was poured into a test tube. The successive addition of two to three shavings of magnesium and three drops of isoamyl alcohol. In the presence of flavonoids, an intense pink-orange or purple color appears.

### Testing for presence of saponosides

This test is based on the property of aqueous solutions containing saponosides to foam when stirred. A volume of 15 mL of the extract was placed in a tube, the tube was shaken vertically for ten seconds and then allowed to stand for ten minutes. After this resting period, the height of the foam is measured. If the height is greater than 1 cm, saponosides are present.

### Testing for presence of tannins

To the residue of five milliliters of the evaporated extract, 15 mL of STIASNY reagent (30% formalin, concentrated HCl:

1/0.5) was added. The whole was placed in a water bath at 80°C for 30 min. The observation of precipitates in large flakes after cooling indicates the presence of tannins.

### Testing for presence of sterols

A volume of 5 mL of the extract was evaporated to dryness in a porcelain capsule in a sand bath. The residue was dissolved hot in 1 mL of acetic anhydride. The whole was inverted into a test tube to which 0.5 mL of concentrated sulfuric acid was added.

### Testing for presence of quinones

Two (2) mL of the extract are evaporated to dryness in a sand bath in a porcelain capsule, then triturated with 5 mL of 1/5 dilute hydrochloric acid. The whole is placed in a boiling water bath for 30 minutes. After cooling, the solution is added to 20 mL of chloroform in a test tube. The chloroform phase is then saturated with 0.5 mL of half-strength ammonia.

### Statistical analysis

All experimental measurements were performed in triplicate and tests were subjected to ANOVA using Statistica version 7.1 software. In case of unequal variance, a Tukey post ANOVA test was performed to determine the homogeneity groups.

## RESULTS AND DISCUSSION

### Results

**Yield:** The extraction carried out on 20 g of *M. morindoides* leaves powder allowed to determine the yields. The dichloromethane and ethyl acetate extracts of *M. morindoides* leaves gave a yield of 3.01% and 3.91%, respectively.

**Cytotoxicity activity:** Figure 1 shows two dose-response curves. Between 0.1 µg/mL and 5 µg/mL, cells viability is 100% for two extracts. From 5 µg/mL to 20 µg/mL, cell viability was approximately 50% for ACE fe.Mm extract. At the same percentage of viability (50%), the concentrations were 100 µg/mL to 150 µg/mL for DCM fe.Mm extract. 10% live cells are observed between 20 µg/mL and 200 µg/mL for ACE fe.Mm and at 200 µg/mL for DCM fe.Mm. At the level of 1% DMSO, the viability is 100% between 0.1 µg/mL and 90 µg/mL. This viability decreases to 60% between 100 and 200 µg/mL.

DCM fe.Mm extract showed toxicity to HCT-116 with an IC50 of 51.14 ± 0.01 µg/mL, while ACE fe.Mm extract showed toxicity with an IC50 of 16.38 ± 0.2 µg/mL (Figure 1). The ACE.fe.Mm extract seems to have a good dose-response on the cells.

<figure><img src="image_8.png" /><figcaption>Figure 1: Dose-response activity of *M. morindoides* leaves extracts on HCT-116.</figcaption></figure>

a) Dose-response activity of ACE fe.Mm extract -b) Dose-response activity of DCM fe.Mm extract.
Antioxidant activity

DPPH test

Figure 2 shows the percentage inhibition of the DPPH radical by vitamin C and the tested extracts in an increasing concentration range. An inhibition of about 92% was obtained by ascorbic acid at concentrations between 50 µg/mL and 100 µg/mL. While the maximum inhibition percentage obtained by the extracts is 59% for the dichloromethane extract and 62% for the ethyl acetate extract.

Therefore, to better understand the antioxidant power of the extracts studied, the IC50 values were determined. The IC50 values of ascorbic acid and the extracts are shown in Figure 3. The IC50 of ascorbic acid was 7.31 ±0.2 µg/mL, that of dichloromethane extract was 52.44 ±4.1 µg/mL and that of ethyl acetate was 39.70 ±1.7 µg/mL. The analyses show that there is a significant difference in the different values (p < 0.05).

<figure><img src="image_9.png" /><figcaption>**Figure 2:** Evolution of percentages of radical inhibition by ascorbic acid, *M. morindoides* leaves extracts.</figcaption></figure>

<figure><img src="image_10.png" /><figcaption>**Figure 3:** IC50 values of ascorbic acid and *M. morindoides* leaves extracts.</figcaption></figure>

The letters a, b, c, mean that there is a significant difference between the extracts and the control.

ABTS+• test

Figure 4 shows the percentages of inhibition of the ABTS radical by gallic acid and tested extracts with an increasing concentration range from 12.5 µg/mL to 200 µg/mL. An inhibition of about 96% was obtained by gallic acid at concentrations between 100 µg/mL and 200 µg/mL with an IC50 value of 25.72 µg/mL. While the maximum inhibition

percentage obtained by the extracts is 86.76 µg/mL for the dichloromethane extract and 60.42 µg/mL for the ethyl acetate extract.

The IC50 values were plotted as histograms (Figure 5). Statistical analysis shows that there is a significant difference between these values (p < 0.05).
<figure><img src="image_11.png" /><figcaption>**Figure 4:** Evolution of percentages of radical inhibition by Gallic acid *M. morindoides* leaves extracts.</figcaption></figure>

<figure><img src="image_12.png" /><figcaption>**Figure 5:** IC50 values of ascorbic acid and *M. morindoides* leaves extracts. The letters a, b, c, mean that there is a significant difference between the extracts and the control</figcaption></figure>

Qualitative characterization of secondary metabolites

Phytochemical screening makes it possible to highlight the different chemical constituents of plant extracts. The result of this phytochemical screening is summarized in Table I. It indicates the presence or absence of a group of secondary

metabolites. It varies very little from one extract to another. But in general, the two extracts (dichloromethane and ethyl acetate) didn't contain alkaloids, saponosides, sterols & terpenes, and tannins but contained polyphenols, flavonoids, and quinones.

<table><caption>**Table I:** Phytochemical constituents of extracts.</caption><thead><tr><th rowspan="2">Compounds</th><th>Ethyl acetate extract</th><th>Dichloromethane extract</th></tr><tr><th>(ACE fe.Mm)</th><th>(DCM fe.Mm)</th></tr></thead><tbody><tr><td>Alkaloids</td><td>-</td><td>-</td></tr><tr><td>Flavonoids</td><td>+</td><td>+</td></tr><tr><td>Polyphenols</td><td>+</td><td>+</td></tr><tr><td>Saponosides</td><td>-</td><td>-</td></tr><tr><td>Sterols & terpenes</td><td>-</td><td>-</td></tr><tr><td>Tannins</td><td>-</td><td>-</td></tr><tr><td>Quinones</td><td>+</td><td>-</td></tr></tbody></table>

+: Presence; -: Absence
DISCUSSION

The use of medicinal plants as an approach to the prevention and treatment of cancer has been followed for many years. Numerous studies have been conducted and have revealed the anticancer activity of certain plants. In the present study, dichloromethane and acetate ethyl extracts of *M. morindoides* leaves were evaluated for their cytotoxic potential on the colorectal cancer cell line HCT-116. The most effective extract was the acetate extract with an IC50=16.38 µg/mL. That could be due to a significant accumulation of chemical compounds responsible for anticancer activity in the acetate extract compared to that of dichloromethane extract. Many phytochemicals exert their cytotoxic effects by acting as cell cycle and apoptosis regulators as well as anti-inflammatory agents¹³. These results are better than those of who obtained¹ an IC50 of 179 ± 0.81 µg/mL on the same HCT-116 cancer cell line using the methanolic extract of *Eclipta alba*. However, this result is less interesting to that of¹⁴ who obtained an IC50 of 11.86 µg/mL with ethyl acetate extract of *Senna alata* tested on HCT-116 cells. Studies have shown that high levels of reactive oxygen species (ROS) promote an increased risk of developing cancer. Another study showed that patient's cancer was deficient in antioxidants compared to healthy individuals⁴. Therefore, in this study, we decided to also evaluate the oxidative activity of *M. morindoides*. DPPH free radical scavenging test showed that the extracts had an antiradical potential but much lower than ascorbic acid with IC50 of 7.31 ± 0.2 µg/mL; 52.44 ±4.1µg/mL and 39.70 ±1.7 µg/mL for ascorbic acid, dichloromethane extract and ethyl acetate respectively. Despite the fact that the antioxidant activity of the extracts is lower than that of the reference substance, they are still considerable. The difference in activity between the two extracts would be linked to the concentration of active ingredients.

Comparison of the IC50 extracts with those of other ethyl acetate extracts revealed that the antioxidant potential of *M. morindoides* extracts is better than that of other ethyl acetate extracts of *Genista quadriflora* and lower than that of *Ipomoea staphylina*. In fact, and obtained by the same DPPH radical trapping test, the respective IC50 was 61.84 µg/mL for *Genista quadriflora*15 and 35.84 µg/mL for *Ipomoea staphylina*¹⁶.

To confirm the results of the anti-radical efficacy of *M. morindoides* extracts obtained by the DPPH test, a second test based on the ability to trap protons by the ABTS + radical was performed. This test shows that the extracts also inhibit the ABTS radical. This confirms the antioxidant potential of these extracts. These results show that ethyl acetate extract being more polar than dichloromethane, concentrates more chemical constituents and has the capacity to donate hydrogen to a free radical¹⁷. These results are better than those obtained by Kouadio (2022), when evaluating the antioxidant activity of *Turraea heterophylla* *dichloromethane* and ethyl acetate extracts, reported IC50 values of 14.50 ±0.32 mg/mL and 13.69 ± 0.33 mg/mL, respectively.

This activity of *M. morindoides* could be due to the nature of the phytochemicals present in this plant. For this purpose, a qualitative characterization test was carried out to highlight the secondary metabolites found in this plant.

The results of the phytochemical screening carried out on the two extracts of *M. morindoides* for cytotoxic and antioxidant purposes showed almost no variation. Both extracts contain polyphenols and flavonoids. The ethyl acetate extract also contains quinones. These results are somewhat in the same direction as those of Koffi (2013) who, after working on the 70% aqueous and ethanolic extract of *M. morindoides* leaves, highlighted not only the presence of polyphenols and flavonoids but also the presence of tannin, alkaloids, quinones,

sterols and saponosides contained in the leaves of *M. morindoides*. The absence of these chemical families in the two extracts could be explained either by a different testing method¹⁷, or by climatic, agro-pedological and geographical factors ¹⁸ or either the nature of the solvent.

The cytotoxic and antioxidant activity of two extracts could therefore be justified by the presence of these secondary metabolites. Indeed, flavonoids are known for their anti-tumor power against colorectal, stomach, lung, and breast and medulloblastoma cancer. They are capable of inducing cell death and inhibiting the growth of cells produced in colorectal cancer¹⁹ with their reducing power, flavonoids are also capable of scavenging free radicals²¹. According to Boua et al (2013), good activity is due to the presence of phenolic compounds. *M. morindoides* would therefore be a good candidate in the search for anticancer and antioxidant molecules.

CONCLUSION

This study demonstrated the potential antioxidant and cytotoxic activity of ethyl acetate and dichloromethane extracts of *Morinda morindoides* leaves. According to the results obtained in this study, phytochemicals as polyphenols could be the source at the origin these activities justifying its traditional use in the treatment of numerous diseases. The ethyl acetate extract showed the best free radical scavenging activity of DPPH and ABTS, and good cytotoxic activity against colorectal cancer line cells HCT116. These results could provide a solid scientific basis for the research of new anti-tumor compounds.

ACKNOWLEDGEMENTS

We thank the association “ALSACE contre le cancer” which funded this research in the 3BIO team (Biovectorization, Bioconjugation and Biomaterials) at UMR7199 CNRS-University of Strasbourg.

REFERENCES

1. Nelson KV, Nalini K S, Madhusmita S, Hari H, Sudhan C, Pullaiah P, Kanuri SM. In vitro anticancer activity of *Eclipta alba* whole plant extract on colon cancer cell HCT-116. BMC Complementary Medicine and Therapies, 2020; (20):355-358.
https://doi.org/10.1186/s12906-020-03118-9 PMid:33225921
PMCID:PMC7681951

2. Globocan «Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries». https://doi.org/10.3322/caac.21660 PMid:33538338

3. Tayo I, Famojuro TO, Elufioye OA, Olajide MD, Adeboye A. New cytotoxic compounds from the leaves of Caesalpinia benthamiana (Baill.) Herend. & Zarucchi (Fabaceae). Avicenna J Phytoned, 2021; 11 (1): 54-67.

4. Pincemail J, Meurisse M, Limet R, Defraigne JO. Activated oxygen species, antioxidants and cancer, Vessels, Heart, Lungs. (4): 44, 1999.

5. Koffi AE. Study of the antibacterial activity of extracts of Morinda morindoides (Baker) Milne-Redhead (Rubiaceae), on the in vitro growth of clinical strains and environmental strains of Vibrio cholerae O: 1: Félix HOUPHOUËT-BOIGNY University, Abidjan, 2013.

6. Bagre I, Bahi C, Ouattara K, Zirihi G. Botanical study and exploration of the antifungal activity of Morinda morindoides (Baker) Milne-Redh on the in vitro growth of Cryptococcus neoformans. journal of phytotherapy, 2012; 9(2):136-141.
https://doi.org/10.1007/s10298-011-0612-y

7. Koni JM, Bostoen K. Names and uses of useful plants among the Nsong, göteborg africana informal series, 2008; (6) :1404-8523.

8. Konda KM, kabakura M, Mbembe B, Itufa Y, Kavuna M, Mafuta M, Mpoyi K, Ndemankeni I, Kadima K, Kelela B, Ngiuvu V, Bongombola M, Dumu L. Traditional medicinal plants Province of Equateur, DR Congo; 2012, 419 p.
9. Ali-Azouaou S. Evaluation of the anticancer effects of pharmacological compounds on cancer stem cells and their descendants: characterization of molecular mechanisms: University of Strasbourg; 2016.

10. Tepe B., Dimitra D., Atalay S, Munevver S, Moschos P. Antimicrobial and antioxidant activities of the essential oil and various extracts of Salvia tomentosa Miller (Lamiaceae). Chimie alimentaire, 2005;Tome 90 (3):333-340.
https://doi.org/10.1016/j.foodchem.2003.09.013

12. Bonnaud C. Towards a method of recycling and valorization of permanent magnets based on rare earths by electrochemistry in an ionic liquid medium. Thesis in chemical 2017.

13. UĞUR.D., Hatice.G., Fatma.G., Ramazan.M.(2017). Cytotoxic Activities of Certain Medicinal Plants on Different Cancer Cell Lines. Turk J Pharmacology Science 14 (3) :222-230.www.american-jiras.com.
https://doi.org/10.4274/tjps.80299 PMid:32454617
PMCID:PMC7227927

14. Okerenta B M O, Keith S. Ethyl Acetate Extract of Senna alata (L) Roxb Increases Cytotoxicity in the Human Breast, Prostate and Colorectal Cancer Cells. Cancer Treatment Reviews, 2018; 6 (3):44-53. https://doi.org/10.11648/j.jctr.20180603.12

15. Boukaabache R, Boubekri N, Boumaza O, Mekkiou R, Seghiri R, Sarri D, Zama D, Benayache F, et Benayach S. Etude phytochimique de l'extrait d'acétate d'éthyle et de

l'antioxydantactivité de Genistaquadriflora Munby (Fabacées).
Der Pharmacia Lettre, 2013; 5 (6) :56-59, 59 p.

16. Mohammad FS, Amartya B, Karmakar V, Ghosh Arya. Antioxidant activity of Ipomoea staphylina ethyl acetate extract. Medicinal plants » International Journal of Phytomedicines and Related Industries,2022 ;14(1):144-148. https://doi.org/10.5958/0975-6892.2022.00015.6

17. Kouadio K B. Chemical and biological study of the leaves of Turraea heterophylla (Meliaceae), a medicinal plant from the COTE D'IVOIRE: Jean Lorougnon Guédé University of Daloa; 2022

18. Lee KW, Kim YJ, Lee HJ, et Lee CY. Cocoa has more phenolic phytochimicals and higher antioxidant capacity than teas and red wine. Food chemistry, 2003 ;(51) :7292-7295.
https://doi.org/10.1021/jf0344385 PMid:14640573

19. Emeraux E. Biological properties of flavonoids: bibliographic study and evaluation of antioxidant activity: University of Lorraine; 2009

20. Boua BB, Mamyrbékova B, Akhanovna J, Kouamé BA et Bekro YA. Criblage phytochimique et potentiel érectile de Turraea heterophylla de Côte d'Ivoire. Journal of applied BioSciences, 2013; (68) :5394-5403. https://doi.org/10.4314/jab.v68i0.95065

21. Pessel F. Eco-compatible synthesis of glucose-functionalized flavonoids as potential antioxidants. Doctoral student(s): Chemistry doctoral school of Paris-Sud (Orsay, Essonne; 2006-2015); 2013.