RESUMEN
This case report aims to highlight a rare and severe presentation of Legionnaires' disease complicated by thrombotic thrombocytopenic purpura (TPP). The patient, a 75-year-old male with a history of COVID-19 infection, presented with bilateral pneumonia positive for Legionella pneumophila. He developed signs of TTP, cerebral hemorrhage, and renal failure. Despite treatment, the patient's condition deteriorated, leading to flaccid paralysis, absent reflexes, and multiple brain hemorrhages. This case suggests a potential autoimmune mechanism for the neurological symptoms seen in this combination of Legionnaires' disease and TTP. Thus, it would be worthwhile to further investigate and understand the relationship between these two conditions. Further research into underlying mechanisms will contribute to improving therapeutic approaches for this rare presentation. Additionally, the patient's previous COVID-19 infection could have contributed to thrombotic complications due to its association with respiratory infections, warranting further investigation.
RESUMEN
Combining the hybridization and repurposing strategies, six compounds from our in-house library and having a designed hybrid structure of MBX-1162, pentamidine and MMV688271 were repurposed as potential antibacterial agents. Among, compounds 1a and 1d elicited potential sub-µg ml-1 activity against the high-priority antibiotic-resistant Gram-positive members of ESKAPE bacteria as well as antibiotic-susceptible Gram-positive bacteria. Furthermore, they showed potential low µg ml-1 activity against the explored critical-priority antibiotic-resistant Gram-negative members of ESKAPE bacteria. In time-kill assay, compound 1a has effective 0.5 and 0.25 µg ml-1 antibacterial lethal concentrations against MRSA in exponential growth phase. In silico investigations predicted compounds 1a and 1d as inhibitors of the open conformation of undecaprenyl diphosphate synthase involved in bacterial isoprenoid synthesis. In addition, compounds 1a and 1d were predicted as inhibitors of NADPH-free but not NADPH-bound form of ketol-acid reductoisomerase and may also serve as potential B-DNA minor groove binders with possible differences in the molecular sequence recognition. Overall, compounds 1a and 1d are presented as multifunctional potential antibacterial agents for further development against high- and critical-priority Gram-positive and Gram-negative antibiotic-resistant ESKAPE bacterial pathogens as well as antibiotic-susceptible Gram-positive bacterial pathogens.
RESUMEN
The continuing need for the discovery of potent antibacterial agents against antibiotic-resistant pathogens is the driving force for many researchers to design and develop such agents. Herein, we report the design, synthesis, and biological evaluation of amidine derivatives as new antibacterial agents. Compound 13d was the most active in this study against a wide range of antibiotic-resistant, and susceptible, Gram-positive, and Gram-negative bacterial strains. Time-kill assay experiments indicated that compound 13d was an effective bactericidal compound against the tested organisms at the log-phase of bacterial growth. Docking simulations were performed to assess in silico its mode of action regarding UPPS, KARI, and DNA as potential bacterial targets. Results unveiled the importance of structural features of compound 13d in its biological activity including central thiophene ring equipped with left and right pyrrolo[2,3-b]pyridine and phenyl moieties and two terminal amidines cyclized into 4,5-dihydro-1H-imidazol-2-yl functionalities. Collectively, compound 13d represents a possible hit for future development of potent antibacterial agents.