TY - JOUR
T1 - Synthesis of acetylenic 17α-ethynylestradiol derivatives as potential trypanocidal oral drugs
T2 - In vitro and in silico evaluation
AU - Juárez-Niño, Elia Donají
AU - Moreno-Rodríguez, Adriana
AU - Juárez-Chávez, Laura
AU - Santillan, Rosa
AU - Ochoa, Ma Eugenia
AU - Argueta-Figueroa, Liliana
AU - Torres-Rosas, Rafael
AU - Domínguez-Diaz, Luis Roberto
AU - Soto-Castro, Delia
N1 - Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2023/2/15
Y1 - 2023/2/15
N2 - The cross-coupling Sonogashira reaction of 17α-ethynylestradiol (EE2) with 4-iodobenzoic acid and 1-iodo-4-nitrobenzene to give two new derivatives 1 and 2, along with the 17α-(4-aminophenyl)ethynyl-estra-1,3,5(10)-triene-3,17β-diol 3 is reported. The compounds were characterized using 1D and 2D NMR techniques, FTIR in the solid state, mass spectrometry and elemental analysis. The correlation in the HMBC spectrum between the acetylenic carbon signal at 85.7 ppm and the aromatic protons at 7.50 ppm, and the presence of the IR bands at 3700–2300, 2217, and 1694 cm−1, support clearly the formation of compound 1. Similarly, the correlation in the HMBC spectrum between the signals at 84.8 and 7.63 ppm, and the IR bands at 2218, 1518, 1339, 818 and 749 cm−1 support the obtention of compound 2. According to the in silico absorption, distribution, metabolism, excretion (ADME) properties of EE2 derivatives, they could act as drugs for oral and topic administration, with gastrointestinal absorption, and good bioavailability. The trypanocidal activity of compounds 1, 2, and 3 was evaluated in vitro against the epimastigote stage of three T. cruzi strains, Ninoa, TH, and INC5, and their cytotoxicity over the J774.2 macrophage cell line was assayed. Derivative 1 showed higher trypanocidal activity than Benznidazole and Nifurtimox against epimastigotes of Ninoa strain, whereas the INC5 strain showed high sensitivity to EE2. None of the compounds showed antibacterial or antifungal activity. Nonetheless, compound 1 could represent an alternative to current trypanocidal drugs.
AB - The cross-coupling Sonogashira reaction of 17α-ethynylestradiol (EE2) with 4-iodobenzoic acid and 1-iodo-4-nitrobenzene to give two new derivatives 1 and 2, along with the 17α-(4-aminophenyl)ethynyl-estra-1,3,5(10)-triene-3,17β-diol 3 is reported. The compounds were characterized using 1D and 2D NMR techniques, FTIR in the solid state, mass spectrometry and elemental analysis. The correlation in the HMBC spectrum between the acetylenic carbon signal at 85.7 ppm and the aromatic protons at 7.50 ppm, and the presence of the IR bands at 3700–2300, 2217, and 1694 cm−1, support clearly the formation of compound 1. Similarly, the correlation in the HMBC spectrum between the signals at 84.8 and 7.63 ppm, and the IR bands at 2218, 1518, 1339, 818 and 749 cm−1 support the obtention of compound 2. According to the in silico absorption, distribution, metabolism, excretion (ADME) properties of EE2 derivatives, they could act as drugs for oral and topic administration, with gastrointestinal absorption, and good bioavailability. The trypanocidal activity of compounds 1, 2, and 3 was evaluated in vitro against the epimastigote stage of three T. cruzi strains, Ninoa, TH, and INC5, and their cytotoxicity over the J774.2 macrophage cell line was assayed. Derivative 1 showed higher trypanocidal activity than Benznidazole and Nifurtimox against epimastigotes of Ninoa strain, whereas the INC5 strain showed high sensitivity to EE2. None of the compounds showed antibacterial or antifungal activity. Nonetheless, compound 1 could represent an alternative to current trypanocidal drugs.
KW - ADME properties
KW - Bacteria
KW - Candida albicans
KW - Hormones
KW - Sonogashira reaction
KW - T. cruzi
UR - http://www.scopus.com/inward/record.url?scp=85142431196&partnerID=8YFLogxK
U2 - 10.1016/j.molstruc.2022.134431
DO - 10.1016/j.molstruc.2022.134431
M3 - Artículo
AN - SCOPUS:85142431196
SN - 0022-2860
VL - 1274
JO - Journal of Molecular Structure
JF - Journal of Molecular Structure
M1 - 134431
ER -