Mononuclear and tetranuclear alkali metal complexes: Synthesis, structural characterization, and in vitro anti-cancer and antimicrobial studies

Shah, Syed Raza; Shah, Zarbad; Khan, Ajmal; Yahya, Saira; Chishti, Arif Ali; Hussain, Javid; Karim, Amir; Anwar, Muhammad U.; Al‐Harrasi, Ahmed

doi:10.1016/j.molstruc.2022.132506

Cited by 1 publication

(2 citation statements)

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“…Metallodrugs of transition metals have been extensively studied but there are insufficient data to decipher the untapped potential of alkali metal complexes, especially against Acinetobacter baumannii ( 44 ). So, this study examined a lithium complex based on 1,10-phenanthroline (phen) and salicylic acid (non-steroidal anti-inflammatory drug) for antimicrobial potential against clinically isolated multi-drug-resistant A. baumannii ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

“…Hence, in this study, lithium complex based on salicylic acid and 1,10-phenanthroline has been explored for its potency against multi-drug-resistant A. baumannii (MDRAB) through different experimental approaches. Its synthesis and structure have already been reported previously ( 28 ). As little has been explored regarding the potential mechanism of action against Gram-negative pathogens, proteomic analysis has been employed to decipher it against A. baumannii .…”

Section: Introductionmentioning

confidence: 98%

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In vitro and in vivo antimicrobial potential of lithium complex against multi-drug resistant Acinetobacter baumannii

Zehra,

Usmani,

Shafiq

et al. 2023

Microbiol Spectr

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Acinetobacter baumannii is a Gram-negative pathogen, accountable for lethal nosocomial infections, owing to high pathogenicity and multi-drug resistance (MDR). Hence, the World Health Organization has prioritized this bacterium against which new pharmacophores are required urgently. Therefore, this study evaluates the antimicrobial potential of lithium complex based on salicylic acid, and 1,10-phenanthroline {[Li(phen) 2 sal]} against MDR A. baumannii (MDRAB) through growth inhibition, growth curve assay, biofilm inhibition, and eradication alongside microscopy. The mechanism of action was proposed by flow cytometry and proteomic analysis. Moreover, in vivo efficacy was assessed using an A. baumannii -induced pneumonia model in mice. Results showed that lithium complex significantly inhibited the bacterial growth at 16–32 µg/mL. Growth kinetics revealed that it retarded the bacterial growth after 2–3 h of treatment. Lithium complex significantly inhibited and reduced >70% of biofilms at the MIC level which is a key problem of indwelling and prosthetic devices. Light and atomic force microscopy further indicated disarticulated biofilm and ruptured cellular membrane post-lithium complex treatment. Proteomic analysis revealed that the compound exerted oxidative stress on A. baumannii which may contribute to cell rupturing. Data are available via ProteomeXchange with identifier PXD044293. Flow cytometry confirmed its role in cytoplasmic membrane disintegration. The lithium complex ameliorated the pneumonia symptoms at non-toxic doses of 20 and 40 mg/kg in the pre-clinical A. baumannii -induced pneumonia model as evident by the significant reduction in bacterial burden and parenchymal inflammation. Taken together, these findings suggest that the lithium complex can be a potential drug candidate against MDRAB. IMPORTANCE Multi-drug resistance (MDR) by virtue of evolving resistance and virulence mechanisms among A. baumannii is a global concern which is responsible for lethal hospital-acquired infections. Therefore, it is crucial to develop new therapeutics against it. Metal complexes are compact structures with diverse mechanisms that the pathogens cannot evade easily which make them a strong drug candidate. In this study, we assessed the in vitro and in vivo efficacy of lithium complex {[Li(phen) 2 sal]} against biofilm-forming MDR A. baumannii . The lithium complex displayed strong antimicrobial activity and reduced the pre-formed mature biofilm which is key barrier for antimicrobial action. Moreover, it employs oxidative stress as one of its mode of actions and causes cellular rupturing. Lithium complex was non-toxic and was significantly effective to overcome pneumonia in mice model. These results highlight the untapped potential of metal complexes that can be explored and utilized for combating notorious A. baumannii infections.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%