Synthesis, in vitro cytotoxicity activity against the human cervix carcinoma cell line and in silico computational predictions of new 4-arylamino-3-nitrocoumarin analogues

• Published in: Journal of molecular structure 2020-01, Vol.1200, p.127047, Article 127047
• Main Authors: Halawa, Ahmed H., Eliwa, Essam M., Hassan, Ahmed A., Nassar, Hesham S., El-Eisawy, R.A., Ismail, Mohamed, Frese, Marcel, Shaaban, Mohamed, El-Agrody, Ahmed M., Bedair, Ahmed H., Sewald, Norbert
• Format: Article
• Language: English
• Subjects: 4-Arylamino-3-nitrocoumarin; Cervical cancer; Cytotoxic activity; In silico computational predictions; Top1-DNA complex
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2019.127047

A new series of 4-arylamino-3-nitrocoumarin analogues (4–18) have been synthesized and characterized by sophisticated spectroscopic techniques (1H NMR, 13C NMR) and mass spectrometry. All the new synthesized compounds were evaluated for their in vitro cytotoxic activity against the human cervix carcinoma cell line (KB-3-1) using resazurin assay with (+)-griseofulvin as the positive control (IC50 = 19 μM). Among them, thiazolidinylidene derivative 17a that bearing malononitrile unit displayed the best cytotoxic potency with IC50 value of 21 μM. Also, in silico docking simulation studies were conducted on human DNA topoisomerase 1 (Top1) (PDB: 1T8I) to explore and interpret the interaction pattern between the selected compounds and target enzyme as well confirm the acquired cytotoxicity results. In addition to the above, in silico predictions of physicochemical properties, ADME (absorption, distribution, metabolism and excretion) parameters, oral toxicity and indication of toxicity targets were implemented for some title compounds. [Display omitted] •New 3-nitrocoumarin analogues were synthesized and characterized by 1D NMR and MS.•Compounds were assayed as a cytotoxic agents toward KB-3-1 using resazurin method.•Compound 17a demonstrated the best cytotoxic potency with IC50 value of 21 μM.•Compound 17a showed high binding affinity of 10.09 kcal/mol to the Top1-DNA complex.•Compound 17a passed the filter of Lipinski's rule and have low oral toxicity.