Identification of new drug candidates against Borrelia burgdorferi using high-throughput screening

• Published in: Drug design, development and therapy development and therapy, 2016-04, Vol.10 (Issue 1), p.1307-1322
• Main Authors: Pothineni, Venkata Raveendra, Wagh, Dhananjay, Babar, Mustafeez Mujtaba, Inayathullah, Mohammed, Solow-Cordero, David, Kim, Kwang-Min, Samineni, Aneesh V, Parekh, Mansi B, Tayebi, Lobat, Rajadas, Jayakumar
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibiotics; Bacterial diseases; Bactiterglo assay; Borrelia burgdorferi; Borrelia burgdorferi - drug effects; Borrelia burgdorferi - growth & development; Cancer; Chemical compounds; Cognitive ability; Deoxyribonucleic acid; DNA; Dose-Response Relationship, Drug; Drug development; Drugs; High-throughput screening; High-Throughput Screening Assays; high-throughput screening persisters; Humans; Lyme disease; Lyme Disease - drug therapy; Microbial Sensitivity Tests; Minimum inhibitory concentration; Muscles; Organic chemistry; Original Research; Pain; Pharmacology; Primates; Regulatory agencies; Researchers; Rodents; Screening; Signs and symptoms; Small Molecule Libraries - chemistry; Small Molecule Libraries - pharmacology; Structure-Activity Relationship; Vector-borne diseases; Zoonoses
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S101486

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