Synthesis and biological evaluation of 2,4,6-trinitroaniline derivatives as potent antitumor agents

Prodrugs for Nitroreductase Based Cancer Therapy‐5: Development of Trinitroaniline Prodrugs/Ssap‐NtrB Combinations for Liver Cancer Using Intracellular and Extracellular Conditions

“…Similarly, ethyl containing bis(2,4,6-trinitrophenyl) alkane diamine derivative (comp. 12) in our previous study [13] were found moderately toxic on Hep3B, PC3, and HT-29 as a drug, butyl containing TNA6 derivative in this study showed good toxicity (IC 50 : 2.809 μM) on Hep3B as a prodrug. In addition, prodrugs TNA4-5 and TNA7 were also found more effective than CB1954 at intracellular Hep3B conditions.…”

“…Chemistry Some trinitroaniline derivatives (TNA1-8) as nitro group containing prodrug candidates were synthesized in different ways and characterized with various spectral techniques (FT-IR, 1 H NMR, 13 C NMR, and MS) in this study (Figure 1, 2 and Supporting Information). Different functional groups were used for the target compounds and investigated their prodrug ability through enzymatic and cytotoxic activity studies.…”

“…So, their detailed cytotoxic activity studies, including cell cycle progression, apoptosis, metastatic effect, and cancer drug abilities, were investigated. [13] Prodrugs TNA1-5 were synthesized from picryl chloride and aliphatic, aromatic, or heterocyclic amines (cyclohexylamine, benzylamine, 2,4-dinitroaniline, piperidine, and morpholine) using different bases (Et 3 N, NaHCO 3, or K 2 CO 3 ) via aromatic nucleophilic substitution reaction with mild yields, 38-78 % (Figure 1). As revealed in Figure 2, prodrugs TNA6-8 were obtained from picryl chloride and diaminoalkane derivatives (1,4-diaminobutane, 1,3-diaminocyclohexane, and 1,4-diaminocyclohexane) using triethylamine as a base at room temperature for 6-24 h with high yields (72-93 %).…”

“…It should be noted that some N-substituted-2,4,6trinitroaniline derivatives containing ethyl, isopropyl, phenyl, 3nitro/4-nitro/3-methoxy/3,5-difluoro phenyl, 1-/2-naphthyl, 4nitrobenzyl, methyl isoxazole groups were synthesized in our previous study, and they could not be considered as prodrug candidates due to showing various levels of toxicity on different cancer cells. [13] Among the bis(2,4,6-trinitrophenyl) alkane diamine (TNA6-8) derivatives, butyl group bearing TNA6 and 1,4-cyclohexyl unit bearing TNA8 have low interaction with enzyme, TNA7 which have 1,3-cyclohexyl group did not interact with the enzyme in limited reaction times. However, IC 50 values of TNA6-8 on Hep3B cancer cells were found as 2.809 μM, 1.640 nM, and 5.068 μM, respectively.…”

“…saprophyticus), in 2012 and synthesized various nitro functional group-containing prodrug candidates, and investigated their enzymatic and cytotoxic effects so far. [8][9][10][11][12][13] Herein, we synthesized trinitroaniline derivatives (TNA1-8) as nitro group containing prodrug candidates by nucleophilic substitution reaction with various experimental conditions and characterized using spectral techniques FT-IR, 1 H NMR, 13 C NMR, and MS. They were also tested for cytotoxic activity against four different human cancer cell lines, Human Hepatocellular Carcinoma (Hep3B), Human Prostate Cancer (PC3), Human Colon Adenocarcinoma (HT-29), and Human Osteosarcoma (Saos-2) and a healthy cell line Human Umbilical Vein (HUVEC) via MTT assay.…”