Bacteria: Drug Resistance Spreads, but Few New Drugs Emerge

Shekhar, Chandra

doi:10.1016/j.chembiol.2010.05.006

Cited by 8 publications

(10 citation statements)

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“…Compounds 4 a-i were afforded through a condensation reaction of aminoguanidine hydrochloride to 3 ai in the presence of a few drops of concentrated hydrochloric acid in ethanol as a solvent. [29] The structures of the compounds 4 a-i were characterized by IR, 1 H-NMR, 13 C-NMR, and mass spectroscopy. The IR spectral data revealed the formation of the C=C in 3 a-i through the appearance of new bands between 2191-2120 cm À 1 .…”

Section: Chemistrymentioning

confidence: 99%

New Phenylthiazoles: Design, Synthesis, and Biological Evaluation as Antibacterial, Antifungal, and Anti‐COVID‐19 Candidates

Shahin,

Mohamed,

Taher

et al. 2023

Chemistry & Biodiversity

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The combination of antibacterial and antiviral agents is becoming a very important aspect of dealing with resistant bacterial and viral infections. The N‐phenylthiazole scaffold was found to possess significant anti‐MRSA, antifungal, and anti‐COVID‐19 activities as previously published; hence, a slight refinement was proposed to attach various alkyne lipophilic tails to this promising scaffold, to investigate their effects on the antimicrobial activity of the newly synthesized compounds and to provide a valuable structure–activity relationship. Phenylthiazole 4 m exhibited the most potent anti‐MRSA activity with 8 μg/mL MIC value. Compounds 4 k and 4 m demonstrated potent activity against Clostridium difficile with MIC values of 2 μg/mL and moderate activity against Candida albicans with MIC value of 4 μg/mL. When analyzed for their anti‐COVID‐19 inhibitory effect, compound 4 b emerged with IC50=1269 nM and the highest selectivity of 138.86 and this was supported by its binding score of −5.21 kcal mol−1 when docked against SARS‐CoV‐2 M pro. Two H‐bonds were formed, one with His164 and the other with Met49 stabilizing phenylthiazole derivative 4 b, inside the binding pocket. Additionally, it created two arene‐H bonds with Asn142 and Glu166, through the phenylthiazole scaffold and one arene‐H bond with Leu141 via the phenyl ring of the lipophilic tail.

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Section: Chemistrymentioning

confidence: 99%

New Phenylthiazoles: Design, Synthesis, and Biological Evaluation as Antibacterial, Antifungal, and Anti‐COVID‐19 Candidates

Shahin,

Mohamed,

Taher

et al. 2023

Chemistry & Biodiversity

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“…Yellow solid; mp 178 °C (dichloromethane-n-hexane); UV-vis: λ max (MeOH)/nm 212 (ε/dm 3 mol −1 cm −1 14 000), 256 (12 600), 343 (8000); IR (KBr): ν max /cm −1 3380 (NH), 1610 (CvO), 1580, 1560, 1340, 1245, 1215, 1080; 1 H NMR (300 MHz, CDCl 3 ): δ 3.93 (s, 3H, OMe), 4.00 (s, 3H, OMe), 6.23 (s, 1H, H5), 7.08 (d, J = 2.4 Hz, H2), 7.30-7.37 (m, 2H, ArH), 7.43-7.51 (m, 2H, ArH), 10.29 (s, 1H, NH); 13 C NMR (75 MHz, CDCl 3 ): δ 55. 6,55.8 (OMe), 87.8 (C7), 98.6 (CCl 3 ), 98.8 (C5), 110.9 (C3), 118.7 (ArC), 121.7 (C2), 127.9, 130.9 (ArCH), 132.2, 133.9, 139.9, 160.5, 161.5 (ArC), 182.5 (CvO); MS (EI): m/z 435 (M + 2, Cl 37/37 , 7%), 433 (M, Cl 35/35 , 15), 316 (33), 314 (100).…”

Section: General Procedures For the Synthesis Of 7-trichloroacetylind...mentioning

confidence: 99%

“…1 Unfortunately, the over-use of antibiotics has resulted in the rapid development of drug-resistant bacterial strains. [2][3][4][5][6] Most of the antibiotic classes in common use today were discovered between 1945 and 1960, during the "Golden Era" of antibiotics, but since that time only a few more new classes of antibiotics have been developed. 6 Moreover, the discovery and development of new antibacterial agents has decreased at an alarming rate in recent years.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4][5][6] Most of the antibiotic classes in common use today were discovered between 1945 and 1960, during the "Golden Era" of antibiotics, but since that time only a few more new classes of antibiotics have been developed. 6 Moreover, the discovery and development of new antibacterial agents has decreased at an alarming rate in recent years. 1,7 In the absence of new antibacterial drugs, antibiotic resistance threatens to pose a grave threat to human health in the coming years.…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, there is a clear and urgent need for the discovery and development of novel classes of antibiotics and drug targets that can slow the rate of appearance of resistance. 6 Bacterial RNA polymerase (RNAP) and transcription are promising targets that have been exploited for the development of novel antimicrobials. There are two forms of bacterial RNAP called core and holoenzyme, and transcription consists of three main sequential stages: initiation, elongation and termination.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and biological activity of novel bis-indole inhibitors of bacterial transcription initiation complex formation

Mielczarek

Devakaram

et al. 2014

Org. Biomol. Chem.

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The increasing resistance of bacteria against clinically approved antibiotics is resulting in an alarming decrease in therapeutic options for today's clinicians. We have targeted the essential interaction between bacterial RNA polymerase and σ(70)/σ(A) for the development of lead molecules exhibiting a novel mechanism of antibacterial activity. Several classes of structurally related bis-indole inhibitors of bacterial transcription initiation complex formation were synthesized and their antimicrobial activities were evaluated. Condensation of indole-7- and indole-2-carbohydrazides with 7- and 2-trichloroacetylindoles or indole-7- and indole-2-glyoxyloyl chlorides resulted in the successful synthesis of 7,7'-, 2,2'-, 2,7'- and 3,2'-linked bis-indole derivatives with -CO-NH-NH-CO- and -CO-CO-NH-NH-CO- linkers. Indole-7-glyoxyloyl chlorides were reacted with hydrazine hydrate in different ratios to afford respective -CO-CO-NH-NH-CO-CO- bis-indole or hydrazide derivatives. The resulting compounds were found to be active against the β'-CH-σ(70)/σ interaction in ELISA assays and inhibited the growth of both Gram-positive and Gram-negative bacteria. Structure-activity relationship (SAR) studies were performed in order to identify the structural features of the synthesized inhibitors required for biological activity.

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The One‐Stop Integrated Nanoagent Based on Photothermal Therapy for Deep Infection Healing and Inflammation Inhibition

Wang,

Gao,

et al. 2023

Advanced Materials

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Chronic wounds caused by bacterial infections have become a major challenge in the medical field. Hypoxia condition in the chronic wound area extremely induces the generation of reactive oxygen species (ROS) and up‐regulates the expression of hypoxia‐inducible factor (HIF‐1α), both of which can enhance the production of pro‐inflammatory M1 subtype macrophages while reducing the anti‐inflammatory M2 subtype macrophages. Besides, the bacteria‐formed biofilms in the chronic wound area also hinder the penetration of therapeutic agents. Encouraged by the natural motors automatically executing tasks, we hypothesize that supplying sufficient oxygen (O2) would simultaneously drive therapeutic agent movement, rescue the hypoxic microenvironment, and disrupt the vicious cycle of inflammation. Here, we develop small organic molecule‐based nanoparticles (2TT-mC6B@Cu5.4O NPs) that possess high photothermal conversion efficiency and enzymatic activities, including superoxide dismutase‐, catalase‐, and glutathione peroxidase‐like activity. 2TT-mC6B@Cu5.4O NPs exhibit superior ROS scavenging and O2 production abilities in synergistically relieving inflammatory microenvironment and deep penetration of 2TT-mC6B@Cu5.4O NPs in the chronic wound tissues. By combining the photothermal property, 2TT-mC6B@Cu5.4O NPs can effectively eliminate bacteria in biofilms to promote wound healing. Furthermore, transcriptome analysis and in vivo experiments further demonstrate that 2TT-mC6B@Cu5.4O NPs effectively inhibit biological activities inside bacteria and alleviate hypoxia in deep tissue infections.This article is protected by copyright. All rights reserved

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Bacteria: Drug Resistance Spreads, but Few New Drugs Emerge

Cited by 8 publications

References 0 publications

New Phenylthiazoles: Design, Synthesis, and Biological Evaluation as Antibacterial, Antifungal, and Anti‐COVID‐19 Candidates

New Phenylthiazoles: Design, Synthesis, and Biological Evaluation as Antibacterial, Antifungal, and Anti‐COVID‐19 Candidates

Synthesis and biological activity of novel bis-indole inhibitors of bacterial transcription initiation complex formation

The One‐Stop Integrated Nanoagent Based on Photothermal Therapy for Deep Infection Healing and Inflammation Inhibition

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