Development of Biphenylthiazoles Exhibiting Improved Pharmacokinetics and Potent Activity Against Intracellular <i>Staphylococcus aureus</i>

Hagras, Mohamed; Abutaleb, Nader S.; Elhosseiny, Noha M.; Abdelghany, Tamer M.; Omara, Mariam; Elsebaei, Mohamed M.; Alhashimi, Marwa; Norvil, Allison B; Gutay, Mark I; Gowher, Humaira; Attia, Ahmed S.; Seleem, Mohamed N.; Mayhoub, Abdelrahman S.

doi:10.1021/acsinfecdis.0c00137

Cited by 14 publications

(13 citation statements)

References 49 publications

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“…After 4 h, the rats were euthanized with an overdose of anesthesia, followed by cervical dislocation, and their skin was dissected out. After washing the skin with Millipore water, the amount of thymol in a homogenized skin sample was measured by HPLC [ 48 ].…”

Section: Methodsmentioning

confidence: 99%

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Thymol-Loaded Eudragit RS30D Cationic Nanoparticles-Based Hydrogels for Topical Application in Wounds: In Vitro and In Vivo Evaluation

et al. 2022

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Natural medicines formulated using nanotechnology-based systems are a rich source of new wound-treating therapeutics. This study aims to develop thymol-loaded cationic polymeric nanoparticles (CPNPs) to enhance the skin retention and wound healing efficacy of thymol. The developed materials exhibited entrapment efficiencies of 56.58 to 68.97%, particle sizes of 36.30 to 99.41 nm, and positively charged zeta potential. In Vitro sustained release of thymol up to 24 h was achieved. Selected thymol CPNPs (F5 and C2) were mixed with methylcellulose to form hydrogels (GF5 and GC2). An In Vivo skin-retention study revealed that GF5 and GC2 showed 3.3- and 3.6-fold higher retention than free thymol, respectively. An In Vitro scratch-wound healing assay revealed a significant acceleration in wound closure at 24 h by 58.09% (GF5) and 57.45% (GC2). The potential for free thymol hydrogel, GF5, and GC2 to combat MRSA in a murine skin model was evaluated. The bacterial counts, recovered from skin lesions and the spleen, were assessed. Although a significant reduction in the bacterial counts recovered from the skin lesions was shown by all three formulations, only GF5 and GC2 were able to reduce the bacterial dissemination to the spleen. Thus, our study suggests that Eudragit RS30D nanoparticles-based hydrogels are a potential delivery system for enhancing thymol skin retention and wound healing activity.

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Section: Methodsmentioning

confidence: 99%

“…Infection of the skin was carried out in accordance with Hagras et al [ 48 ]. Briefly, BALB/c mice were divided into five groups (n = 5/group), and their backs were shaven by a clipper.…”

Section: Methodsmentioning

confidence: 99%

Thymol-Loaded Eudragit RS30D Cationic Nanoparticles-Based Hydrogels for Topical Application in Wounds: In Vitro and In Vivo Evaluation

et al. 2022

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“…While the antimicrobial is being depleted out of the world, everyone should have his responsibility to help against the antimicrobial resistance. In our lab, the investigation to find a good antibacterial started with the phenylthiazole, which was initially discovered as a thiazole core bearing a guanidine head and alkyl chain tail [12][13][14][15][16][17][18][19]. Lately, this scaffold has been intensively investigated and optimized to improve its activity and metabolic profile.…”

Section: Introductionmentioning

confidence: 99%

Arylpyrazole as selective anti‐enterococci; synthesis and biological evaluation of novel derivatives for their antimicrobial efficacy

Sayed

Abutaleb

Kotb

et al. 2022

Journal of Heterocyclic Chem

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Exploring the structure–activity relationships (SAR) of a new set of phenylpyrazoles unveiled a potential anti‐enterococcus lead compound 12. The benzofuran moiety linked to the phenylpyrazole 12 was 32 times better than vancomycin against Enterococcus faecalis ATCC 51299. Besides, compound 12 is expected to have an excellent oral bioavailability according to the in silico studies. Of SAR analysis, we found that the benzofuran side chain was essential for the activity. Changing the benzofuran with either benzothiophene, phenyl, pyridinyl, tolyl, or naphthyl reduces/nullifies the pharmacological action. Besides the anti‐enterococcal activity, derivatives 4 and 6 can be used to develop new broad‐spectrum antibiotics as they exhibited activity against the wild‐type highly virulent Escherichia coli isolate. Moreover, compound 13 was proved to show antifungal activity (MIC = 4 μg/ml) against the Candida albicans SS5314 (wild type). Finally, the in silico analysis showed that those compounds have good profiles regarding the absorption, distribution, metabolism, and excretion studies, drug‐likeness and pharmacokinetics properties.

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“…(Khameneh, Diab, Ghazvini, & Fazly Bazzaz, 2016) In our lab, we began by investigating the use of phenylthiazole as a potential new antimicrobial agent. (M. M. Mohamed M Elsebaei et al, 2019;Elsebaei et al, 2018; M. M. Hagras et al, 2020;Hosny et al, 2020;Mancy et al, 2019;Mohammad et al, 2014). (El-Gamal, Sherbiny, & El-Morsi, 2015).…”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of Novel Terremide and Sulfonaides Derivatives for Pharmacological Evaluation

Helal

Hussien

Elsebaei

et al. 2022

Al-Azhar Journal of Pharmaceutical Sciences

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Bacterial infections were first recorded back at 3000 B.C.E. Since then, there have been an enormous number of pandemics that hit the world. Countless doctors and researchers have been working on a definitive solution to exterminate all bacterial infections of all kinds. Marine microorganisms have been widely used as a valid source for pharmacologically active components, and recently the amount of metabolites produced by marine-derived fungi have been increased magnificently, which provided not only wide spectrum of highly active compounds but also gave an enormous number of opportunities for chemists to modify theses incredible entities into more effective and less harmful compounds that can be used as cytotoxic, antiviral, antibacterial and antifungal agents. (He et al., 2013) Quinazolines have been spotted as a new group of agents of decent promising and potential chemotherapeutic and antimicrobial activities. (Raghavendra, Gurubasavarajaswamy, Nagaranavile, & Parameshwaran, 2009) The structure activity relationship of quinazolines has shown it has a very weak antimicrobial activity,(Alafeefy, 2009) Close inspection of the structure-activityrelationships (SAR) of quinazolines revealed important structural features necessary for their antimicrobial activity: a nitrogenous ring and a side chain. Quinazoline heterocyclic compounds have been used to synthesize compounds like terremide B to enhance the activity. Currently, advantageous moieties have been combined to generate new hybrid scaffolds of quinazoline with the objective of synthesizing new moieties enhancing the biological activity and drug-like properties.

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Development of Biphenylthiazoles Exhibiting Improved Pharmacokinetics and Potent Activity Against Intracellular Staphylococcus aureus

Cited by 14 publications

References 49 publications

Thymol-Loaded Eudragit RS30D Cationic Nanoparticles-Based Hydrogels for Topical Application in Wounds: In Vitro and In Vivo Evaluation

Thymol-Loaded Eudragit RS30D Cationic Nanoparticles-Based Hydrogels for Topical Application in Wounds: In Vitro and In Vivo Evaluation

Arylpyrazole as selective anti‐enterococci; synthesis and biological evaluation of novel derivatives for their antimicrobial efficacy

Design and Synthesis of Novel Terremide and Sulfonaides Derivatives for Pharmacological Evaluation

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