Synthesis and Biological Evaluation of New Amino Acid and Dipeptide Derivatives of Neocryptolepine as Anticancer Agents

Abstract

The syntheses of neocryptolepine derivatives containing an amino acid or a dipeptide at the C-9 position and their evaluation for antitumor activity in vitro and in vivo are reported. To establish the influence of an amino acid or a peptide on the physicochemical properties of 5H-indolo[2,3-b]quinoline (DiMIQ), lipophilic and hemolytic properties were investigated. Most of the compounds displayed a high antiproliferative activity in vitro and strongly inhibited growth of tumor in mice compared to cyclophosphamide. The attachment of the hydrophilic amino acid or the peptide to the hydrophobic DiMIQ increased its hydrophilic properties and decreased its hemolytic activity. The glycylglycine conjugate (7a) was the most promising derivative. It strongly inhibited the growth of the tumor in mice (at dose 50 mg kg(-1) day(-1) it inhibited the tumor growth by 46-63% on days 11-16 and by 29-43% on days 18-23) and significantly decreased hemolytic activity and lowered the in vivo toxicity compared to DiMIQ.

Synthesis, molecular docking, ctDNA interaction, DFT calculation and evaluation of antiproliferative and anti-Toxoplasma gondii activities of 2,4-diaminotriazine-thiazole derivatives

“…Unbound dye was removed by rinsing (4×) in 1% acetic acid. The protein-bound dye was extracted with 10 mM unbuffered Tris base (Sigma-Aldrich, Germany) for determination of the optical density ( λ = 540 nm) in a computer-interfaced, 96-well Synergy H4 (BioTek Instruments USA) photometer microtiter plate reader (Sidoryk et al 2012 ).…”

“…Twenty microliter of MTT solution (MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, stock solution: 5 mg/ml) was added to each well and incubated for 4 h. After the incubation time was complete, 80 µl of the lysis mixture was added to each well (lysis mixture: 225 ml dimethylformamide, 67.5 g sodium dodecyl sulfate and 275 ml of distilled water). The optical densities of the samples were read after 24 h on a Synergy H4 (BioTek Instruments USA) photometer microtiter plate reader at 570 nm (Sidoryk et al 2012 ). All of chemicals were obtained from Sigma-Aldrich, Germany.…”

Synthesis of Thiol Derivatives of Biological Active Compounds for Nanotechnology Application

“…In the present study, an efficient method of thiol-group introduction to the structure of common natural products and synthetic active compounds with recognized biological efficacy such as: genistein ( 1 ), 5,11-dimethyl-5 H -indolo[2,3-b]quinolin ( 2 ), capecitabine ( 3 ), diosgenin ( 4 ), tigogenin ( 5 ), flumethasone ( 6 ), fluticasone propionate ( 7 ), ursolic acid methyl ester ( 8 ), and β-sitosterol ( 9 ) was developed ( Figure 1 ). According to the literature, compounds 1 – 9 and their respective derivatives show anticancer [ 11 , 12 , 13 ], antibacterial [ 14 ], antifungal [ 15 ], and anti-inflammatory [ 13 , 15 , 16 ] activities. Some of them are widely used in therapy as the registered drugs: flumethasone [ 17 ], fluticasone propionate [ 18 ], and capecitabine [ 19 , 20 ].…”

Synthesis and Biological Evaluation of a Series of Novel Celastrol Derivatives with Amino Acid Chain

“…Recently, it was became a research hot‐spot in medicinal chemistry that many natural products with good biological activities and drugs were modified by various amino acids, amino acids derivatives and some oligopeptides . Firstly, many amino acids were considered as the prefect carriers of prodrugs base on they are more biological compatibility and less toxicity; secondly, some amino acids participate in regulating of gene expression, protein‐synthesis and signaling pathways, such as arginine, glutamine, leucine, tryptophan, threonine; then the metabolic activities of the cancers cell are more vigorous, frequent and greater demand for amino acids than the normal cell lines; finally, most oral drugs were absorbed by intestinal epithelial cells, in which various membrane transporters are more distributed and higher expressed, including oligopeptide transporter protein and amino acid transporters .…”