Asymmetric synthesis and study of biological activity of (epi-)benzoanalogues of bioactive phenanthroquinolizidine alkaloids

Screening of Phenanthroquinolizidine Alkaloid Derivatives for Inducing Cell Death of L1210 Leukemia Cells with Negative and Positive P-glycoprotein Expression

“…N -methylthienoquinolizinium iodides A4 , B9 , and B10 were obtained by N -alkylation of the corresponding thienoquinolizidines 10Bb , 11Ba , and 11Bb [23]. The asymmetric synthesis of (epi)-benzo analogs of the phenanthroquinolizidine bioactive alkaloids (-)-cryptopleurine and (-)-(15R)-hydroxycryptopleurine 5a , 5b , 6a , 7a , 7b , 9 , 10 and 11 (BQD) (Table 1) was achieved from enantiopure L-2-aminoadipic acid and benzaldehyde [14]. Details about the synthesis, accepted structure and characterization are published elsewhere [13,14,23].…”

“…Due to their efficacy, both derivatives were assayed on the human acute myeloid leukemia SKM-1 and MOLM-13 cells, and their respective IC 50 values were similar to those obtained for S, R and T cells, i.e., approximately 60–90 μΜ for derivative 9 and 10–15 μΜ for derivative 11 . In our previous paper [14], the cytotoxic effects induced by derivatives 9 and 11 were tested with two non-neoplastic cell lines (hamster kidney fibroblast cell line BHK-21 and African green monkey kidney fibroblast-like cell line VERO). Derivative 11 reached the IC 50 value in the higher concentration range of 213 µM for BHK-21 cells and 266 µM for VERO cells.…”

“…For this reason, we have oriented ourselves to study the effective means of cell death induced by phenanthroquinolizidine alkaloid derivatives related to P-gp expression in leukemia cells. We used sets of 13 TQDs, 3 of which are N -methylthienoquinolizinium iodides, and 8 BQDs (Table 1) for which the synthesis and chemical characterization have been described elsewhere [13,14,23]. Only derivative 11Ba was effective from among all the TQD in S cells (with IC 50 ≈ 130 μM).…”

“…In the present paper, we report the cytotoxic effects of a set of cryptopleurine derivatives (thienoquinolizidine derivatives and (epi-)benzo analogs with bioactive phenanthroquinolizidine alkaloids) obtained by organic synthesis [13,14] on the lymphocytic leukemia cell line L1210. When looking for new active structures with potential antileukemic activity, it is important to think about the potential risks of multidrug resistance (MDR) development.…”

Crystal, molecular and electronic structure of (5S,11R,11aS)-11-hydroxy-5-methyl-1,2,3,4,5,6,11,11a-octahydropyrido[1,2-b]isoquinolin-5-ium iodide

“…The title compound, (5S,11R,11aS)-11-hydroxy-5-methyl-1,2,3,4,5,6,11,11a-octahydro-pyrido[1,2b]isoquinolin-5-ium iodide, was prepared according to a standard protocol described in literature (Pagáč et al, 2018).…”