Synthesis and Pharmacophore Modeling of Naphthoquinone Derivatives with Cytotoxic Activity in Human Promyelocytic Leukemia HL-60 Cell Line

Abstract

Catalyst/HypoGen pharmacophore modeling approach and three-dimensional quantitative structure-activity relationship (3D-QSAR)/comparative molecular similarity indices analysis (CoMSIA) methods have been successfully applied to explain the cytotoxic activity of a set of 51 natural and synthesized naphthoquinone derivatives tested in human promyelocytic leukemia HL-60 cell line. The computational models have facilitated the identification of structural elements of the ligands that are key for antitumoral properties. The four most salient features of the highly active beta-cycled-pyran-1,2-naphthoquinones [0.1 microM < IC50 < 0.6 microM] are the hydrogen-bond interactions of the carbonyl groups at C-1 (HBA1) and C-2 (HBA2), the hydrogen-bond interaction of the oxygen atom of the pyran ring (HBA3), and the interaction of methyl groups (HYD) at the pyran ring with a hydrophobic area at the receptor. The moderately active 1,4-naphthoquinone derivatives accurately fulfill only three of these features. The results of our study provide a valuable tool in designing new and more potent cytotoxic analogues.

Antiparasitic activities of novel ruthenium/lapachol complexes

“…Because of its antiproliferative activity, lapachol has been employed as a prototype for the design and synthesis of new anticancer and antimicrobial agents. This has led to the identification of fewer lapachol derivatives with an enhanced activity [9][10][11][12].…”

Ciclização do lapachol induzida por sais de tálio III

“…As naftoquinonas, de modo geral, representam uma importante classe de produtos naturais, [1][2][3] com uma grande variedade de atividades biológicas, das quais podemos citar as atividades anticancer, [4][5][6][7] antivirus, 8,9 antibacteriana, 10 antimalarial 11,12 e antifúngica. 13 O lapachol (1) e seus derivados, como, por exemplo, a α-xiloidona (deidro-α-lapachona) (2) e a deidro-iso-α-lapachona (3), são naftoquinonas naturais isoladas das cascas das árvores da família Bignoneacea, como a Tabebuia spp., [1][2][3] Haplophragma adenophylum, 14 Oroxylum indicum (L.) Vent, 15 Newbouldia laevis Seem., 16 Radermachera sinica Hemsl 17 e mais recentemente da Catalpa ovata; 18 enquanto a rinacantina-A (4) foi isolada em 1988 da Rhinacanthus nasutus (L.) Kurz (Acanthaceae).…”

Synthesis and biological assessment of novel acylhydrazone derivatives of 2-methyl-1,4-naphthoquinone

“…[6][7][8][9][10][11][12] Thus, the naphthoquinone acylhydrazones 6a-m were assessed for their anticancer effects against MCF-7 and HCT116 cell lines using MTT viability assay. The results of the compounds after 24 h of treatment are summarized in Figure 6.…”

“…1 A multitude of naturally occurring naphthoquinones reportedly exhibit a diverse array of biological activities including fungicidal, 2 antibacterial, 3 antiviral, 4 antimalarial, 5 anticancer, 1,[6][7][8][9][10][11][12] in addition to effects that counter inflammation 13 and artherosclerosis.…”