Photoactivated 2,3-distyrylindoles kill multi-drug resistant bacteria

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:28

Article

Edwards, Leslie¹  Turner, Danielle¹  Champion, Cody¹  Khandelwal, Megha¹  Zingler, Kailee¹  Stone, Cassidy²  Rajapaksha, Ruwini D.²  Yang, Jing³  Ranasinghe, Mahinda, I²  Kornienko, Alexander²  Frolova, Liliya, V²  Rogelj, Snezna¹ 

[1] New Mexico Inst Min & Technol, Dept Biol, 801 Leroy Pl, Socorro, NM 87801 USA

[2] New Mexico Inst Min & Technol, Dept Chem, 801 Leroy Pl, Socorro, NM 87801 USA

[3] Univ New Mexico, Dept Chem & Chem Biol, 1 Univ New Mexico, Albuquerque, NM 87131 USA

关键词: Multi-drug resistance;    MRSA;    VRE;    CRE;    Light-activated;    S. mutans;   

DOI  :  10.1016/j.bmcl.2018.04.001

来源: Elsevier

【 摘 要 】

Compounds based on the 2,3-distyrylindole scaffold were found to exhibit bactericidal properties upon irradiation with white light. At the concentration of 1 mu M, the lead compound 1 completely (ca. 10(9) CFU/mL) eradicated such Gram-positive organisms as S. aureus (MRSA, MSSA), E. faecalis (VRE), S. pyogenes and S. mutans when irradiated with white light for 2 min. At the concentration of 5 mu L and in the presence of polymyxin E at non-bactericidal 1.25 mu g/mL concentration, 1 also showed a 7-log to 9-log reductions in bacterial counts of such Gram-negative organisms as multi-drug resistant (MDR) A baumannii, MDR P. aeruginosa, E. coll and Klebsiella pneumoniae (CRE: KPC and NDM-1), also when irradiated with white light for 2 mm The structure-activity relationship studies revealed that unsubstituted at benzene rings 2,3-distyrylindole 2 was most potent and gave a 5-order of magnitude eradication of a MRSA strain at the concentration of 30 nM upon irradiation with white light. Initial mechanistic experiments revealed the disruption of bacterial cell membrane, but indicated that singlet oxygen production, which is commonly associated with photodynamic therapy, may not play a role in the bactericidal effects of the 2,3-distyryhndoles. (C) 2018 Elsevier Ltd. All rights reserved.

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