Comparison of In Vitro Antimelanoma and Antimicrobial Activity of 2,3-Indolo-betulinic Acid and Its Glycine Conjugates

被引：7

作者：

Lombrea, Adelina ^{[1
,2
]}

Semenescu, Alexandra-Denisa ^{[2
,3
]}

Magyari-Pavel, Ioana Zinuca ^{[1
,2
]}

Turks, Maris ^{[4
]}

Luginina, Jevgenija ^{[4
]}

Peipins, Uldis ^{[4
,5
]}

Muntean, Delia ^{[2
,6
]}

Dehelean, Cristina Adriana ^{[2
,3
]}

Dinu, Stefania ^{[7
,8
]}

Danciu, Corina ^{[1
,2
]}

机构：

[1] Victor Babes Univ Med & Pharm Timisoara, Dept Pharmacognosy, Eftimie Murgu Sq 2, Timisoara 300041, Romania

[2] Victor Babes Univ Med & Pharm Timisoara, Res Ctr Pharmaco Toxicol Evaluat, Eftimie Murgu Sq 2, Timisoara 300041, Romania

[3] Victor Babes Univ Med & Pharm Timisoara, Dept Toxicol, Eftimie Murgu Sq 2, Timisoara 300041, Romania

[4] Riga Tech Univ, Inst Technol Organ Chem, Fac Mat Sci & Appl Chem, P Valdena Str 3, LV-1048 Riga, Latvia

[5] Nat Sci Technol Ltd, Rupnicu Str 4, LV-2114 Olaine, Latvia

[6] Victor Babes Univ Med & Pharm Timisoara, Dept Microbiol, Eftimie Murgu Sq 2, Timisoara 300041, Romania

[7] Victor Babes Univ Med & Pharm Timisoara, Fac Dent Med, Dept Pedodont, 9 Revolutiei Bv, Timisoara 300041, Romania

[8] Victor Babes Univ Med & Pharm Timisoara, Fac Dent Med, Pediat Dent Res Ctr, 9 Revolutiei Bv, Timisoara 300041, Romania

来源：

PLANTS-BASEL | 2023年 / 12卷 / 06期

关键词：

2; 3-indolo-betulinic acid; glycine conjugates; melanoma; antibacterial; BETULINIC ACID; BETULONIC ACID; BIOLOGICAL EVALUATION; URSOLIC ACID; CUTANEOUS MELANOMA; CYTOTOXIC ACTIVITY; ANTIVIRAL ACTIVITY; NATURAL COMPOUNDS; RISK-FACTORS; DERIVATIVES;

D O I：

10.3390/plants12061253

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

Malignant melanoma is one of the most pressing problems in the developing world. New therapeutic agents that might be effective in treating malignancies that have developed resistance to conventional medications are urgently required. Semisynthesis is an essential method for improving the biological activity and the therapeutic efficacy of natural product precursors. Semisynthetic derivatives of natural compounds are valuable sources of new drug candidates with a variety of pharmacological actions, including anticancer ones. Two novel semisynthetic derivatives of betulinic acid-N-(2,3-indolo-betulinoyl)diglycylglycine (BA1) and N-(2,3-indolo-betulinoyl)glycylglycine (BA2)-were designed and their antiproliferative, cytotoxic, and anti-migratory activity against A375 human melanoma cells was determined in comparison with known N-(2,3-indolo-betulinoyl)glycine (BA3), 2,3-indolo-betulinic acid (BA4) and naturally occurring betulinic acid (BI). A dose-dependent antiproliferative effect with IC50 values that ranged from 5.7 to 19.6 mu M was observed in the series of all five compounds including betulinic acid. The novel compounds BA1 (IC50 = 5.7 mu M) and BA2 (IC50 = 10.0 mu M) were three times and two times more active than the parent cyclic structure B4 and natural BI. Additionally, compounds BA2, BA3, and BA4 possess antibacterial activity against Streptococcus pyogenes ATCC 19615 and Staphylococcus aureus ATCC 25923 with MIC values in the range of 13-16 mu g/mL and 26-32 mu g/mL, respectively. On the other hand, antifungal activity toward Candida albicans ATCC 10231 and Candida parapsilosis ATCC 22019 was found for compound BA3 with MIC 29 mu g/mL. This is the first report of antibacterial and antifungal activity of 2,3-indolo-betulinic acid derivatives and also the first extended report on their anti-melanoma activity, which among others includes data on anti-migratory activity and shows the significance of amino acid side chain on the observed activity. The obtained data justify further research on the anti-melanoma and antimicrobial activity of 2,3-indolo-betulinic acid derivatives.

引用

页数：21