Synthesis of 5-(4-(1H-phenanthro[9,10-d]imidazol-2-yl)benzylidene)thiazolidine-2,4-dione as promising DNA and serum albumin-binding agents and evaluation of antitumor activity

• Published in: European journal of medicinal chemistry Vol. 166; pp. 267 - 280
• Main Authors: Singh, Iqubal, Rani, Richa, Luxami, Vijay, Paul, Kamaldeep
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 15-03-2019
• Subjects: Acenaphthoimidazole; Anticancer agents; DNA intercalation; Molecular modelling; Phenanthroimidazole; Serum albumin; Acenaphthoimidazole; Serum albumin; Phenanthroimidazole; Molecular modelling; Anticancer agents; DNA intercalation
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2019.01.053

A series of phenanthro[9,10-d]imidazole/oxazole and acenaphtho[1,2-d]imidazole with different aryl groups at C2-position has been synthesized. These compounds were in vitro evaluated for antitumor activity against a panel of 60 human cancer cell lines. Compound 8 exhibits higher cytotoxicity towards leukemia, colon, melanoma, renal, and breast cancer cell lines than the other evaluated cell panels and low toxicity against normal cell line Hek293. The binding properties of compound 8 with DNA have been investigated with absorption, emission and circular dichroism as well as thermal denaturation experiments which indicate intercalation with base pairs of human and calf thymus DNA. The molecular docking and site-selective binding studies also reveal the predominant intercalation of compound 8 in base pairs of DNA. The interaction between thiazolidine based phenanthrene 8 and serum albumins (HSA and BSA), transport proteins, has also been explored which shows quenching of fluorescence through static mechanism. The thermodynamic parameters, obtained from van't Hoff relationship indicate the prevalence of hydrogen-bonding/hydrophobic interactions for the binding phenomenon.
[Display omitted]
•Phenanthro[9,10-d]imidazoles/oxazoles and acenaphtho[1,2-d]imidazoles were synthesized.•Anticancer activities of compounds were evaluated with 60 human cancer cell lines.•Cytotoxicity of compound 8 was studied with human normal cell lines Hek293.•Binding interactions of compound 8 was studied with DNA and serum albumin.•Molecular modelling between compound 8 and DNA indicated considerable interactions.