Rationally designed lawsone derivatives as antimicrobials against multidrug-resistant Staphylococcus aureus

Patent metadata

Field	Value
Publication number	US-12433853-B2
Application number	US-202017637581-A
Country	US
Kind code	B2
Filing date	Aug 26, 2020
Priority date	Aug 26, 2019
Publication date	Oct 7, 2025
Grant date	Oct 7, 2025

Abstract

Naphthoquinone derivatives of Lawsone have been found to be effective against Staphylococcus aureus and methicillin resistant Staphylococcus aureus (MRSA). Such compounds generally contain a substituent group at the 3-position of a specific naphthoquinone compound, i.e. 2-hydroxy-1,4-naphthoquinone. One of these derivatives referred to as compound 6c in the series exhibits potent antimicrobial activity that is comparable to that of the two commercial antibiotics ofloxacin and ciprofloxacin against the two strains of methicillin sensitive Staphylococcus aureus (MSSA; ATCC 29213 and ATCC 6538). In the case of two strains of MRSA (ATCC BAA-44 and ATCC BAA-1717) that have developed drug resistance to both ofloxacin and ciprofloxacin, the antimicrobial activity of 6c can almost rival that of vancomycin and daptomycin. Furthermore, 6c is also effective against vancomycin-intermediate and daptomycin non-susceptible strain of MRSA (ATCC 700699). Besides the efficacy, 6c has a much improved drug resistance profile in comparison with the conventional antibiotics.

First claim

What is claimed is:

1. A method of treating an infected human being and/or animal comprising:
topically administering a composition to said human being and/or animal,
wherein the composition comprises;
one or more compounds having the formula:

where R, independently, comprises CH 2 CH 3 , or (CH 2 ) 3 CH 3 , or (CH 2 ) 5 CH 3 , or (CH 2 ) 7 CH 3 , or any combination thereof,
wherein the composition is capable of inhibiting or reducing the growth of methicillin-sensitive Staphylococcus aureus by at least 1-Log CFU.

2. A method of treating an infected human being and/or animal comprising:
topically or intravenously administering a composition to said human being and/or animal,
wherein the composition comprises:
one or more compounds having the formula:

where R, independently, comprises CH 2 CH 3 , or (CH 2 ) 3 CH 3 , or (CH 2 ) 5 CH 3 , or (CH 2 ) 7 CH 3 , or any combination thereof,
wherein the composition is capable of inhibiting or reducing the growth of methicillin-resistant Staphylococcus aureus by at least 1-Log CFU.

3. The method according to claim 2 , further comprising the step of topically administering the composition to skin or soft tissue of said human being and/or animal at a dose of from about 0.3 mg/kg to about 300 mg/kg.

4. The method according to claim 2 , further comprising the step of topically administering the composition to an infected wound of said human being and/or animal at a dose of from about 0.3 mg/kg to about 300 mg/kg.

5. The method according to claim 2 , further comprising the step of intravenously administrating the composition to said human being and/or animal at a dose of from about 0.3 mg/kg to about 300 mg/kg.

6. The method according to claim 2 , further comprising the step of topically administering to skin or soft tissue of said human being and/or animal the composition in combination with one or more of oxacillin, ofloxacin, ciprofloxacin, vancomycin, or daptomycin.

7. The method according to claim 2 , further comprising the step of topically administering to an infected wound of said human being and/or animal the composition in combination with one or more of oxacillin, ofloxacin, ciprofloxacin, vancomycin, or daptomycin.

8. The method according to claim 2 , further comprising the step of intravenously administering to skin or soft tissue of said human being and/or animal the composition in combination with one or more of oxacillin, ofloxacin, ciprofloxacin, vancomycin, or daptomycin.

Assignees

• Univ Kent State Ohio

Inventors

• Kim Min-Ho
• Huang Songping D
• Song Ronghui
• Yu Bing

Classifications

• C07C45/74

  combined with dehydration · CPC title

• A61K38/14

  Peptides containing saccharide radicals; Derivatives thereof {, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin} · CPC title

• A61K31/5383

  ortho- or peri-condensed with heterocyclic ring systems · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• A61K31/431

  containing further heterocyclic rings, e.g. ticarcillin, azlocillin, oxacillin · CPC title