Screening and Molecular Docking of Novel Benzothiazole Derivatives as Potential Antimicrobial Agents

Abstract

The burden of antibiotic resistance necessitates a continued search for new antimicrobials. We evaluated the antimicrobial activities of novel benzothiazoles synthesized by our group. Antibacterial activity was evaluated in vitro in Staphylococcus aureus, Bacillus subtilis, and Escherichia coli, while the antifungal activity was tested in Candida albicans and Aspergillus niger, and expressed as the minimum inhibitory concentration (MIC; µg/mL). MIC values of benzothiazole compounds ranged from 25 to 200 µg/mL. Compounds 3 and 4 gave high antibacterial and moderate antifungal activities, while 10 and 12 showed moderate activity against all tested organisms. In addition, some benzothiazole compounds significantly suppressed the activity of Escherichia coli dihydroorotase and inhibited the dimorphic transition of Candida albicans. Moreover, the active benzothiazole compounds induced DNA and protein leakage in Aspergillus niger spores. Molecular interactions of benzothiazole derivatives with dihydroorotase revealed the formation of hydrogen bonds with the active site residues LEU222 or ASN44. Strong hydrophobic interactions of the bulky thiazole and naphthalene rings at the entrance to the active site might interfere with the access of substrates to their binding sites, which results in dihydroorotase inhibition. Thus, inhibition of dihydroorotase might contribute to the observed antimicrobial actions of these compounds.

Exploration of the Antimicrobial Effects of Benzothiazolylthiazolidin-4-One and In Silico Mechanistic Investigation

“…We have replaced 6-trifluoromethoxy substituent of benzothiazole ring first by 6-CN, 6-Ad, 4-Me-6-Ad and after by 4-OCH3, and 6-Cl keeping the same substitution at position 4 of benzene ring mostly for 6-Cl, 4-OMe and in some cases of 6-CN (Figure 2). Thus, we synthesized 2-(2-(substituted phenyl)-4-oxothiazolidin-3yl)benzo [d] (15)(16)(17)(18)(19).…”

“…It is worth mentioning that benzothiazole is a privileged heterocyclic scaffold with multiple applications and tremendous range of pharmacological activity. Benzothiazoles are recognized for their anti-inflammatory [ 12 , 13 , 14 ], antimicrobial [ 15 , 16 , 17 , 18 , 19 ], anesthetic [ 20 ], anticancer [ 21 , 22 , 23 ], anti-viral [ 24 , 25 , 26 ], analgesic [ 13 , 14 ], antipyretic [ 27 ], antidiabetic [ 28 , 29 , 30 ], antioxidant [ 12 , 16 , 20 , 21 , 31 ], carbonic anhydrize inhibitory [ 26 , 32 , 33 ], anticonvulsive [ 34 , 35 ], antifungal [ 33 , 36 , 37 ] and many other [ 38 , 39 ] activities. Additionally, the benzothiazole scaffold is present in three FDA approved drugs ( Figure 1 ).…”

Concise Synthesis of Some New Benzothiazole‐Based Heterocycles as Probable Anticancer and Antioxidant Agents

“…Benzothiazole derivatives have fascinating interest due to their varied biological activities viz. antioxidant, anti‐inflammatory, [2] neuroprotective, [3] anti‐proliferative, [4] anti‐diabetic, [5] antimicrobial, [6] antitumor, [7] analgesic, [8] anti‐gastric cancer, [9] anticonvulsant, [10] antinociceptive, [11] anti‐tubercular, [12] anthelmintic, [13] antiviral, [14] histamine H 3 antagonist, [15] appetite depressants, [16] and muscle relaxant [17] activities. In addition, the anticancer action of benzothiazole compounds has been extensively applied in recent years [18] .…”

New Insights into Antibacterial Compounds: From Synthesis and Discovery to Molecular Mechanisms of Action

“…Two papers in this special issue present two approaches to optimize the antimicrobial activity of compounds previously described as having antimicrobial activity. The paper by Morsy et al describes the experimental screening of antimicrobial activities of benzothiazole derivatives against selected bacteria and fungi [4]. The studies were complemented by computer-assisted molecular docking studies, as benzothiazoles were previously demonstrated to inhibit Escherichia coli dihydroorotase [4].…”

“…The paper by Morsy et al describes the experimental screening of antimicrobial activities of benzothiazole derivatives against selected bacteria and fungi [4]. The studies were complemented by computer-assisted molecular docking studies, as benzothiazoles were previously demonstrated to inhibit Escherichia coli dihydroorotase [4]. In order to gain new insights into the structure/antimicrobial activity relationships, Alves et al synthesized cyclam derivatives, mono-and trans-disubstituted with benzyl, methylbenzyl, trifluoromethylbenzyl, or trifluoroethylbenzyl moieties appended to the macrocyclic ring nitrogen atoms [5].…”