1-Phenyl-8-[[4-(pyrrolo[1,2-a]quinoxalin-4-yl)phenyl]methyl]-1,3,8-triazaspiro[4.5]decan-4-one: Synthesis, Crystal Structure and Anti-Leukemic Activity

Abstract

1-Phenyl-8-[[4-(pyrrolo[1,2-a]quinoxalin-4-yl)phenyl]methyl]-1,3,8-triazaspiro[4.5]decan-4-one has been successfully synthesized via a multi-step pathway starting from 2-nitroaniline. Structure characterization of this original pyrrolo[1,2-a]quinoxaline derivative was achieved by FT-IR, 1H-NMR, 13C-NMR, X-Ray and HRMS spectral analysis. This title compound shows interesting cytotoxic potential against several human leukemia cell lines (K562, HL60, and U937 cells).

Synthesis, Crystal Structure and Anti-Leukemic Activity of 1,3-Dihydro-1-{1-[4-(4-phenylpyrrolo[1,2-a]quinoxalin-3-yl)benzyl]piperidin-4-yl}-2H-benzimidazol-2-one

“…Among them, the pyrrolo[1,2-a]quinoxalines were common motifs, with a broad range of pharmacological properties, and could be considered as a privileged substructure for drug design [1,2]. Such nitrogen-containing valuable heterocyclic compounds have been previously described as antipsychotic agents [3], antiviral agents [4], adenosine receptor modulators [5], antituberculosis agents [6,7], antiprotozoal agents [8][9][10][11][12][13][14] and anticancer agents [15][16][17][18][19]. The discovery of novel and original anti-cancer derivatives is one of the most important goals in pharmaceutical chemistry.…”

“…In the course of our work, that has been devoted to discovering new heterocyclic pyrroloquinoxaline compounds employed in cancer chemotherapy, we previously identified the 1,3-dihydro-1-{1-[4-(3-phenylpyrrolo[1,2-a]quinoxalin-4-yl)benzyl]piperidin-4-yl}-2Hbenzimidazol-2-one JG576 as being endowed with interesting activity towards various human leukemia cells [18]. This anti-leukemic pyrroloquinoxaline derivative JG576 was previously reported as a new structural analogue of derivative A6730 (Figure 1), a reference Protein kinase B (PKB, also known as Akt) inhibitor that presents antiproliferative activity against several human leukemia cell lines [15][16][17][18][19].…”

“…In this context, and as an extension of our research work on the development of novel anticancer pyrrolo [1,2-a]quinoxaline heterocyclic drugs, we decided to further substitute our valuable nitrogen heterocyclic pharmacophore. Thus, taking into account our experience in the field of the synthesis of new bioactive heterocyclic derivatives based on this pyrrolo[1,2-a]quinoxaline heterocyclic scaffold [8][9][10][11][12][13][14][15][16][17][18][19], we use our previously described anti-leukemic JG576 moiety (Figure 1) [18] as a template for the design and synthesis of a new compound in which the benzylpiperidinyl benzimidazolone and phenyl substituents were inverted between the positions 3 and 4 of the pyrrolo[1,2-a]quinoxaline moiety. Consequently, we report herein on the synthesis and structural identification of the 1,3-dihydro-1-{1-[4-(4-phenylpyrrolo[1,2-a]quinoxalin-3-yl)benzyl]piperidin-4-yl}-2Hbenzimidazol-2-one 9.…”

“…This original substituted pyrrolo[1,2-a]quinoxalines 9 is then tested against three leukemia cell lines, namely: K562, U937 and HL60. [8][9][10][11][12][13][14][17][18][19]. The Suzuki-Miyaura cross-coupling reaction of this synthesized 4-chloropyrroloquinoxaline 5 with phenylboronic acid performed in the presence of Pd(PPh 3 ) 4 as a catalyst, and in the presence of sodium carbonate used as the base, gave the 4-phenylpyrrolo[1,2-a]quinoxaline 6.…”

Design, synthesis, and antiproliferative effect of 2,9‐bis[4‐(pyridinylalkylaminomethyl)phenyl]‐1,10‐phenanthroline derivatives on human leukemic cells by targeting G‐quadruplex

“…In the course of our work devoted to the discovery of new heterocycles for use in anticancer chemotherapies, [ 18–23 ] we previously designed and prepared a series of new substituted 2,9‐bis[(substituted‐aminomethyl)phenyl]‐1,10‐phenanthroline derivatives A (Figure 1), which were designed to bind to DNA G‐quadruplexes [ 24,25 ] and endowed with interesting activity toward human leukemia cells. [ 24 ] In this context and by considering the biological activities of these previous 2,9‐bis[(substituted‐aminomethyl)phenyl]‐1,10‐phenanthrolines against human leukemic cells, we have undertaken the synthesis of a new series of 2,9‐bis[(substituted‐aminomethyl)phenyl]‐1,10‐phenanthroline derivatives 1a – i .…”