RT info:eu-repo/semantics/article
T1 Withanolide-Type Steroids fromWithania aristata as Potential Anti-Leukemic Agents
A1 Moujir, Laila M.
A1 Llanos, Gabriel G.
A1 Araujo, Liliana
A1 Amesty, Ángel
A1 López Bazzocchi, Isabel
A1 Jiménez Díaz, Ignacio Antonio
K1 Withania aristata
K1 withasteroids
K1 anti-leukemia activity
K1 structure–activity relationship
K1 drug-likeness prediction
AB Leukemia is a blood or bone marrow cancer with increasing incidence in developed regionsof the world. Currently, there is an ongoing need for novel and safe anti-leukemic agents, as nofully e ective chemotherapy is available to treat this life-threatening disease. Herein, are reportedthe isolation, structural elucidation, and anti-leukemic evaluation of twenty-nine withanolide-typesteroids (1–29) from Withania aristata. Among them, the new isolated withanolides, withaperoxidinsA–D (1–4) have an unusual six-membered cyclic peroxide moiety on the withasteroid skeleton asa structural novelty. Their structures have been elucidated by means of spectroscopic analyses,including 2D NMR experiments. In addition, extensive structure–activity relationships and in silicoADME studies were employed to understand the pharmacophore and pharmacokinetic propertiesof this series of withasteroids. Compounds 15, 16, and 22 together with withaferin A (14) wereidentified as having improved antiproliferative e ect (IC50 ranging from 0.2 to 0.7  M) on humanleukemia HL-60 cell lines compared with the reference drug, etoposide. This cytotoxic potency wasalso coupled with good selectivity index (SI 33.0–9.2) on non-tumoral Vero cell line and in silicodrug likeness. These findings revealed that these natural withasteroids are potential candidates aschemotherapeutic agents in the treatment of leukemia
YR 2020
FD 2020
LK http://riull.ull.es/xmlui/handle/915/35939
UL http://riull.ull.es/xmlui/handle/915/35939
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 09-ago-2024