Submit Manuscript  

Article Details


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

[ Vol. 14 , Issue. 6 ]

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 and Hamid R. Nasiri   Pages 647 - 661 ( 15 )

Abstract:


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.

Affiliation:

Istanbul University, Avcilar, 34320, Istanbul, Chemistry Department, Engineering Faculty, Istanbul University, Avcilar, 34320, Istanbul, Engineering Sciences Department, Engineering Faculty, Istanbul University, Avcilar, 34320, Istanbul, Pharmaceutical Microbiology Department, Pharmacy Faculty, Istanbul University, Beyazit, 34116, Istanbul, Pharmaceutical Microbiology Department, Pharmacy Faculty, Istanbul University, Beyazit, 34116, Istanbul, Department of Pharmaceutical Chemistry, Maharishi Markandeshwar College of Pharmacy, Maharishi Markandeshwar University, Mullana, Ambala 133207, Haryana, Department of Bioorganic Medicinal Chemistry, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Research Institute for Drug Discovery, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Department of Bioorganic Medicinal Chemistry, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Institute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe-University Frankfurt, Max-von-Laue-Straße 7, D-60438 Frankfurt am Main

Graphical Abstract:



Read Full-Text article