Synthesis and Bioactivity Evaluation of N-Arylsulfonylindole Analogs Bearing a Rhodanine Moiety as Antibacterial Agents

Abstract

Due to the rapidly growing bacterial resistance to antibiotics and the scarcity of novel agents under development, bacterial infections are still a pressing global problem, making new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, urgently needed. In this paper, seven series of N-arylsulfonylindole analogs 5–11 bearing rhodanine moieties were synthesized, characterized, and evaluated for antibacterial activity. According to the in vitro antimicrobial results, half of the synthesized compounds showed potent inhibition against four Gram-positive bacteria, with MIC values in the range of 0.5–8 µg/mL. For multidrug-resistant strains, compounds 6a and 6c were the most potent, with MIC values of 0.5 µg/mL, having comparable activity to gatifloxacin, moxiflocaxin and norfloxacin and being 128-fold more potent than oxacillin (MIC = 64 µg/mL) and 64-fold more active than penicillin (MIC = 32 µg/mL) against Staphylococcus aureus ATCC 43300.

5-(1H-Indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl)alkancarboxylic Acids as Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies

“…Another interesting class of heterocyclic compounds is 5-(1H-Indol-3-ylmethylene) -2thioxothiazolidin-4-ones with wide spectrum of biological activities as well. Among them are antitumor [26,27] and antimicrobial [28,29], inhibitors of proteases anthrax lethal factor, inhibitors against neurotoxin type A [28], aldose reductase [30], PIM kinase [31], PI3Kα [32], IKKβ [33], and GSK-3 [34] enzymes.…”

N-Derivatives of (Z)-Methyl 3-(4-Oxo-2-thioxothiazolidin-5-ylidene)methyl)-1H-indole-2-carboxylates as Antimicrobial Agents—In Silico and In Vitro Evaluation

“…All compounds have been assessed for their ADMET profile in ADMET Predictor version 10.4 provided by the Simulation Plus software package [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ...…”

“…So far, many indole-based rhodanine derivatives ( Figure 3 ) have been proposed [ 6 , 41 , 45 , 46 , 47 , 48 , 49 ] as antimicrobial agents, some of which possess high efficacy in treating multi-drug resistant pathogens [ 6 , 41 , 47 , 48 , 49 ]. Therefore, it is noteworthy that the combination of indole and rhodanine scaffolds into new chemical entities could be a promising strategy for antimicrobial therapies.…”

Rhodanine‐Incorporated Indole Derivatives as Pharmacologically Vital Hybrids

“…As the result of the SAR study, there is no significant difference in the antibacterial activity between derivatives with a weak electron‐donating group (R 1 =CH 3 ) and non‐substituted compounds (R 1 =H). Moreover, substituting a halogen atom on an indole ring decreases the activity compared to non‐substituted compounds (R 2 =H) [23] …”