Syed Rasheed

Synthesis and biological evaluation of α-triazolyl chalcones as a new type of potential antimicrobial agents and their interaction with calf thymus DNA and human serum albumin

A series of α-triazolyl chalcones were efficiently synthesized. Most of the prepared compounds showed effective antibacterial and antifungal activities. Noticeably, α-triazolyl derivative 9a exhibited low MIC value of 4 μg/mL against MRSA and Micrococcus luteus, which was comparable or even superior to reference drugs. The further research revealed that compound 9a could effectively intercalate into Calf Thymus DNA to form 9a-DNA complex which might block DNA replication to exert their powerful antimicrobial activities. Competitive interactions between 9a and metal ions to Human Serum Albumin (HSA) suggested the participation of Fe(3+), K(+) and Mg(2+) ions in 9a-HSA system could increase the concentration of free 9a, shorten its storage time and half-life in the blood, thus improving its antimicrobial efficacy.

Synthesis and biological evaluation of a new class of quinazolinone azoles as potential antimicrobial agents and their interactions with calf thymus DNA and human serum albumin

A series of novel quinazolinone azoles were synthesized and characterized by NMR, IR, MS and HRMS spectra. Bioactive assays showed that some target compounds exhibited significant antimicrobial potency. Especially, nitroimidazole derivative 3a displayed comparable or even superior antibacterial efficacies (MIC = 0.03–0.05 μmol mL−1) in contrast with norfloxacin (MIC = 0.01–0.05 μmol mL−1) and chloromycin (MIC = 0.02–0.10 μmol mL−1). The preliminary interactive investigations of compound 3a with calf thymus DNA by UV-vis spectroscopy revealed that compound 3a could bind to DNA to form compound 3a–DNA complex by an intercalative mode and further block DNA replication to exert powerful antibacterial and antifungal activities. Hydrogen bonds and van der Waals forces played important roles in the association of compound 3a–HSA.

Synthesis of tetrazole compounds as a novel type of potential antimicrobial agents and their synergistic effects with clinical drugs and interactions with calf thymus DNA

A series of tetrazole derivatives were synthesized and characterized by NMR, IR, MS and HRMS spectroscopy. The bioactive assay manifested that most of the target compounds exhibited good antifungal activity, especially compound 6g displayed comparable or even stronger antifungal efficiency in comparison with the reference drug Fluconazole. The combination of tetrazole derivative 6g with antibacterials Chloromycin and Norfloxacin, or antifungal Fluconazole respectively was more sensitive to methicillin-resistant MRSA and Fluconazole-insensitive Aspergillus flavus. Further research revealed that compound 6g could effectively intercalate into Calf Thymus DNA to form a 6g–DNA complex which might block DNA replication to exert its good antimicrobial activities.

Design, synthesis, and antibacterial evaluation of novel azolylthioether quinolones as MRSA DNA intercalators

A series of azolylthioetherquinolones was synthesized and characterized by NMR, IR, MS and HRMSspectroscopy. All the newly prepared compounds were screened for their antimicrobial activities. Bioactive assay manifested that most of the azolylthioether quinolones exhibited good antimicrobial activities. Especially, imidazolylthioether quinolone 4e displayed remarkable anti-MRSA and anti-P. aeruginosa efficacies with low MIC values of 0.25 μg mL−1, even superior to reference drugs. They induced bacterial resistance more slowly than clinical drugs. Molecular docking study indicated strong binding interactions of compound 4e with topoisomerase IV–DNA complex, which correlated with the inhibitory effect. The preliminarily interactive investigation of compound 4e with genomic DNA isolated from MRSA revealed that compound 4e could intercalate into MRSA DNA through a copper ion bridge to form a steady 4e–Cu2+–DNA ternary complex which might further block DNA replication to exert the powerful bioactivities.

Design, synthesis, and biological evaluation of novel benzimidazole derivatives and their interaction with calf thymus DNA and synergistic effects with clinical drugs

A series of new benzimidazole derivatives was synthesized and characterized by IR, 1H NMR, 13C NMR, MS, and HRMS spectra. All the new compounds were screened for their antimicrobial activities in vitro by a twofold serial dilution technique. The bioactive evaluation showed that 3,5-bis(trifluoromethyl)phenyl benzimidazoles were comparably or even more strongly antibacterial and antifungal than the reference drugs Chloromycin, Norfloxacin, and Fluconazole. The combination of 2,4-difluorobenzyl benzimidazole derivative 5l and its hydrochloride 7 respectively with the antibacterials Chloromycin, Norfloxacin, and the antifungal Fluconazole was more sensitive to methicillin-resistant MRSA and Fluconazole-insensitive A. flavus. In addition, the interaction of compound 5l with calf thymus DNA demonstrated that this compound could effectively intercalate into DNA to form a compound 5l-DNA complex that might block DNA replication and thereby exert good antimicrobial activity.

Design, Synthesis, and Antimicrobial Evaluation of Novel Quinolone Imidazoles and Interactions with MRSA DNA

A novel series of quinolone imidazoles as new type of antimicrobial agents were synthesized. Most compounds exhibited good bioactivities especially against MRSA even superior to reference drugs. They induced bacterial resistance more slowly than clinical drugs and gave low cytotoxicity to human cells. The pKa values of these compounds showed appropriate ranges to pharmacokinetic behaviors. The interactions between compound 8b, Cu2+ ion, and MRSA DNA revealed that compound 8b could intercalate into DNA through copper ion bridge to form a steady 8b–Cu2+–DNA ternary complex which might further block DNA replication to exert the powerful bioactivities. Study of compound 8b with human serum albumin indicated that compound 8b could be effectively stored and carried by human serum albumin.

Design, synthesis and biological evaluation of amino organophosphorus imidazoles as a new type of potential antimicrobial agents

A series of amino organophosphorus imidazoles were designed and synthesized as a novel structural type of antimicrobial agents. Bioactive evaluation in vitro showed that compound 3f exhibited equipotent or superior anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) and anti-S. cerevisiae efficiencies (minimal inhibitory concentration (MIC)=2 μg/mL) to clinical drugs, and the combinations with antibacterial or antifungal drugs enhanced the antimicrobial efficiency. Highly active molecule 3f showed low propensity for bacteria to develop resistance, and the preliminary action mechanism studies demonstrated that 3f was membrane-active, but had no significant intercalation towards MRSA DNA. The computational study on 3f reasonably explained its high antimicrobial activity. Experimental data revealed that ground-state 3f-HSA complexes were formed mainly through hydrophobic interactions and hydrogen bonds with a spontaneous process, and the non-radioactive energy transfer from HSA to 3f occurred beyond Förster resonance energy transfer theory. The participation of metal ions in 3f-HSA supramolucular system could increase the concentration of free compound 3f, and shorten its storage time and half-life in the blood to improve the maximum antimicrobial efficacy.

CeCl3.7H2O-SiO2 Catalyzed Ultrasonicated Solvent-Free Synthesis of Carbamoyl/Carbamothioyl Phosphonates and Antimicrobial Activity Evaluation

GRAPHICAL ABSTRACT Abstract an expeditious and green method has been developed for the synthesis of a series of P‒C bond derivatives, diethyl substituted phenylcarbamoylphosphonates 6(a–e)/phenylcarbamothioylphosphonates 7(a–f) in high yields via simple addition reaction of isocyanates/isothiocyanates with diethyl phosphite in the presence of silica supported Lewis acid catalyst, SiO2-CeCl3.7H2O under solvent-free and sonication conditions. The advantages of this method are high yields, avoiding of harmful solvents, operational simplicity, shorter reaction time, and recoverability and recyclability of the catalyst. Antimicrobial activity was assayed for the title compounds, whereas the compounds 6c, 7b, and 7e against bacteria, and 6a, 7b, 7c, and 7e against fungi exhibited potential growth of inhibition.