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  • Title: Design, synthesis and antimicrobial evaluation of novel benzimidazole-incorporated sulfonamide analogues.
    Author: Zhang HZ, He SC, Peng YJ, Zhang HJ, Gopala L, Tangadanchu VKR, Gan LL, Zhou CH.
    Journal: Eur J Med Chem; 2017 Aug 18; 136():165-183. PubMed ID: 28494254.
    Abstract:
    A novel series of benzimidazole-incorporated sulfonamide analogues were designed and synthesized with an effort to overcome the increasing antibiotic resistance. Compound 5c gave potent activities against Gram-positive bacteria and fungi, and 2,4-dichlorobenzyl derivative 5g showed good activities against Gram-negative bacteria. Both of these two active molecules 5c and 5g could effectively intercalate into calf thymus DNA to form compound-DNA complex respectively, which might block DNA replication to exert their powerful antimicrobial activity. Molecular docking experiments suggested that compounds 5c and 5g could insert into base-pairs of DNA hexamer duplex by the formation of hydrogen bonds with guanine of DNA. The transportation behavior of these highly active compounds by human serum albumin (HSA) demonstrated that the electrostatic interactions played major roles in the strong association of active compounds with HSA, and which was also confirmed by the full geometry calculation optimizations.
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