ABSTRACT
Our earlier research has shown that N-phenyl-2,2-dichloroacetamide analogues had much higher anti-cancer activity than the lead compound sodium dichloroacetate (DCA). In this current study, a variety of N-arylphenyl-2,2-dichloroacetamide analogues were synthesized via Suzuki coupling reaction and their anti-cancer activity was evaluated. The results showed that N-terphenyl-2,2-dichloroacetamide analogues had satisfactory anti-cancer activity. Among them, N-(3,5-bis(benzo[d][1,3]dioxol-5-yl)phenyl)-2,2-dichloroacetamide (6 k) had an IC(50) of 2.40 µM against KB-3-1 cells, 1.04 µM against H460 cells and 1.73 µM against A549 cells.
Subject(s)
Acetamides/chemistry , Acetamides/chemical synthesis , Antineoplastic Agents/chemical synthesis , Benzodioxoles/chemical synthesis , Drug Design , Acetamides/toxicity , Antineoplastic Agents/chemistry , Antineoplastic Agents/toxicity , Benzodioxoles/chemistry , Benzodioxoles/toxicity , Cell Line, Tumor , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Humans , Structure-Activity RelationshipABSTRACT
Our earlier research has shown that mono-substituted N-phenyl-2, 2-dichloroacetamide exhibited much higher anti-cancer activity than the lead compound sodium dichloroacetate (DCA). In this paper, a variety of multi-substituted N-phenyl-2, 2-dichloroacetamides were synthesized and biologically evaluated. The results showed that 3, 5-disubstituted N-phenyl-2, 2-dichloroacetamide analogues had satisfactory potency. Among them, N-(3, 5-diiodophenyl)-2, 2-dichloroacetamide had an IC50 of 2.84 micromol x L(-1) against non-small cell lung cancer cell line A549 and could induce cancer cell apoptosis.
Subject(s)
Acetamides/chemical synthesis , Antineoplastic Agents/chemical synthesis , Drug Design , Acetamides/chemistry , Acetamides/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Humans , Inhibitory Concentration 50 , Molecular Structure , Structure-Activity RelationshipABSTRACT
A current study shows that sodium dichloroacetate (DCA) can induce cancer cell apoptosis and inhibit tumor growth, but its cytotoxic activity is low (IC(50) > 1000 microM for A549). In this paper, a variety of DCA derivatives were synthesized, and their cytotoxic activities were evaluated. The result showed that the N-phenyl-2,2-dichloroacetamide analogues had satisfactory potencies. Among them, N-(3-iodophenyl)-2,2-dichloroacetamide (3e), an optimized lead compound, has an IC(50) against A549 as low as 4.76 microM. Furthermore, it can induce cancer cell apoptosis and has a low toxicity in mice (LD(50) = 1117 mg/kg).
Subject(s)
Acetamides/chemistry , Acetamides/pharmacology , Acetanilides/chemistry , Acetanilides/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Drug Design , Acetamides/chemical synthesis , Acetamides/toxicity , Acetanilides/chemical synthesis , Acetanilides/toxicity , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/toxicity , Cell Line, Tumor , Female , Humans , Inhibitory Concentration 50 , Lethal Dose 50 , Male , Mice , Structure-Activity RelationshipABSTRACT
In the crystal structure of the title compound, C(11)H(14)ClNO(3), inter-molecular hydrogen bonds link mol-ecules in the ab plane, forming layers that stack along the c axis.
