Synthesis, Computational Study, and Evaluation of In Vitro Antimicrobial, Antibiofilm, and Anticancer Activities of New Sulfanyl Aminonaphthoquinone Derivatives

Author(s): Nilufer Bayrak*, Hatice Yıldırım, Amac Fatih Tuyun*, Emel Mataraci Kara, Berna Ozbek Celik, Girish Kumar Gupta, Halil I. Ciftci, Mikako Fujita, Masami Otsuka, Hamid R. Nasiri

Journal Name: Letters in Drug Design & Discovery

Volume 14 , Issue 6 , 2017

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Background: A set of novel sulfanyl aminonaphthoquinone derivatives (5a-j) were synthesized starting from 2,3-dichloro-1,4-naphthoquinone (1). The amine substituents were introduced via a nucleophilic substitution at reflux temperature. Subsequent reactions of 2-chloro- 3-arylamino-1,4-naphthoquinones (3a-d) with different thiols (4a-c) led to the formation of the desired amino- and thio- substituted products (5a-j).

Methods: The purity and identity of the synthesized compounds were verified with IR, 1H and 13C NMR, and MS spectroscopy. In vitro antimicrobial activity was evaluated in a panel of seven bacterial strains (three Gram-positive and four Gram-negative bacteria) and one fungi with an additional study of antibiofilm activities. The anticancer activities of two selected compounds (5e and 5f) were evaluated against 60 human tumor cell lines derived from nine neoplastic diseases by National Cancer Institute (NCI).

Results: As a result, compound (5e) was identified as a hit with antibacterial efficiency against human originated pathogens S. aureus with minimal inhibitory concentration (MIC) of 19.53 μg/mL. When considering the antibiofilm activities of antibacterial molecule 5e against the S. aureus biofilms, the minimum biofilm eradication concentration (MBEC) value was 10000 μg/mL. Concerning on anticancer activities, both compounds (5e and 5f) exhibited moderate anticancer activities on some of tumor cells, but no activity against normal peripheral blood mononuclear cells (PBMC). In addition, docking study was used to provide further insights into the experimental observations.

Conclusion: Taken together, compound 5e could be considered as a promising starting point for further development.

Keywords: Naphthoquinones, aminoquinones, antibacterial activity, antifungal activity, antibiofilm activity, anticancer activity, NCI, colon cancer, docking study.

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Article Details

Year: 2017
Page: [647 - 661]
Pages: 15
DOI: 10.2174/157018081406170606155530
Price: $65

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