Drug repurposing strategy part 1: from approved drugs to agri-bactericides leads

Abstract

Phytopathogenic bacteria are a major cause of crop mortality and yield reduction, especially in field cultivation. The lack of effective chemistry agri-bactericides is responsible for challenging field prevention and treatment, prompting the development of long-lasting solutions to prevent, reduce, or manage some of the most devastating plant diseases facing modern agriculture today and in the future. Therefore, there is an urgent need to find lead drugs preventing and treating phytopathogenic bacterial infection. Drug repurposing, a strategy used to identify novel uses for existing approved drugs outside of their original indication, takes less time and investment than Traditional R&D Strategies in the process of drug development. Based on this method, we conduct a screen of 700 chemically diverse and potentially safe drugs against Xanthomonas oryzae PV . oryzae ACCC 11602 ( Xoo ), Xanthomonas axonopodis PV . citri ( Xac ), and Pectobacterium atrosepticum ACCC 19901 ( Pa ). Furthermore, the structure-activity relationship and structural similarity analysis of active drugs classify potent agri-bactericides into 8 lead series: salicylanilides, cationic nitrogen-containing drugs, azole antifungals, N -containing group, hydroxyquinolines, piperazine, kinase inhibitor and miscellaneous groups. MIC values were evaluated as antibacterial activities in this study. Identifying highly active lead compounds from the screening of approved drugs and comparison with the currently applied plant pathogenic bactericide to validate the bactericidal activity of the best candidates and assess if selected molecules or scaffolds lead to develop new antibacterial agents in the future. In conclusion, this study provides a possibility for the development of potent and highly selective agri-bactericides leads.

Design and Synthesis of Novel Antimicrobial Agents

“…This approach can bring failed drug back to life and highlight new targets and indications for existing drugs. The advantages of drug repurposing are increasing efficiency, minimizing investment and safety risks, reducing time to FDA approval, and reducing costs for pharmaceutical companies [ 158 , 159 , 160 , 161 , 162 ]. Here, we mention some of repurposed drug for antibacterial use ( Figure 12 ).…”

A redox-responsive macrocycle based on the crown ether C7Te for enhanced bacterial inhibition

“…Disinfectants find wide-ranging applications in the medical and healthcare fields, 1–3 food processing, 4,5 and environmental management. 6,7 Similar to antibiotics, disinfectants are susceptible to the development of antimicrobial resistance (AMR) in bacteria, posing a significantly global health challenge particularly after the COVID-19 pandemic.…”

Repurposing Salicylamides to Combat Phytopathogenic Bacteria and Induce Plant Defense Responses

“…The development of new agrochemical is long-term and expensive, with an average cost of US$ 286 million, and taking 10-12 years. [10][11][12][13] However, the strategy of "repurpose drugs", the development of new uses for existing drugs, can result in significant savings in time and costs. This strategy also has a shorter drug discovery and development timeline, with the discovery and development of new agrochemicals a 10 -to 12year process from the start.…”