Identification of New Drug Candidates Against Borrelia burgdorferi Using High-Throughput Screening

Authors

Venkata Raveendra Pothineni, Stanford University
Dhananjay Wagh, Stanford University
Mustafeez Mujtaba Babar, Stanford University
Mohammed Inayathullah, Stanford UniversityFollow
David Solow-Cordero, Stanford University
K. M. Kim, Stanford University
A. V. Samineni, Stanford University
Mansi B. Parekh, Stanford University
Lobat Tayebi, Marquette UniversityFollow
Jayakumar Rajadas, Stanford UniversityFollow

Document Type

Article

Language

eng

Format of Original

16 p.

Publication Date

4-1-2016

Publisher

Dove Medical Press

Source Publication

Drug Design, Development and Therapy

Source ISSN

1177-8881

Original Item ID

DOI: 10.2147/DDDT.S101486

Abstract

Lyme disease is the most common zoonotic bacterial disease in North America. It is estimated that .300,000 cases per annum are reported in USA alone. A total of 10%–20% of patients who have been treated with antibiotic therapy report the recrudescence of symptoms, such as muscle and joint pain, psychosocial and cognitive difficulties, and generalized fatigue. This condition is referred to as posttreatment Lyme disease syndrome. While there is no evidence for the presence of viable infectious organisms in individuals with posttreatment Lyme disease syndrome, some researchers found surviving Borrelia burgdorferi population in rodents and primates even after antibiotic treatment. Although such observations need more ratification, there is unmet need for developing the therapeutic agents that focus on removing the persisting bacterial form of B. burgdorferi in rodent and nonhuman primates. For this purpose, high-throughput screening was done using BacTiter-Glo assay for four compound libraries to identify candidates that stop the growth of B. burgdorferi in vitro. The four chemical libraries containing 4,366 compounds (80% Food and Drug Administration [FDA] approved) that were screened are Library of Pharmacologically Active Compounds (LOPAC1280), the National Institutes of Health Clinical Collection, the Microsource Spectrum, and the Biomol FDA. We subsequently identified 150 unique compounds, which inhibited .90% of B. burgdorferi growth at a concentration of ,25 µM. These 150 unique compounds comprise many safe antibiotics, chemical compounds, and also small molecules from plant sources. Of the 150 unique compounds, 101 compounds are FDA approved. We selected the top 20 FDA-approved molecules based on safety and potency and studied their minimum inhibitory concentration and minimum bactericidal concentration. The promising safe FDA-approved candidates that show low minimum inhibitory concentration and minimum bactericidal concentration values can be chosen as lead molecules for further advanced studies.

Comments

Published version. Drug Design, Development and Therapy, Vol. 10 (April 1, 2016): 1307-1322. DOI. © 2016 Dove Medical Press. Used with permission.

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License

Recommended Citation

Pothineni, Venkata Raveendra; Wagh, Dhananjay; Babar, Mustafeez Mujtaba; Inayathullah, Mohammed; Solow-Cordero, David; Kim, K. M.; Samineni, A. V.; Parekh, Mansi B.; Tayebi, Lobat; and Rajadas, Jayakumar, "Identification of New Drug Candidates Against Borrelia burgdorferi Using High-Throughput Screening" (2016). School of Dentistry Faculty Research and Publications. 191.
https://epublications.marquette.edu/dentistry_fac/191