Design, synthesis and biological evaluation of new 2-aminothiazole scaffolds as phosphodiesterase type 5 regulators and COX-1/COX-2 inhibitors

Hussein, Abdel Haleem M.; Khames, Ahmed A.; El-Adasy, Abu-Bakr A.; Atalla, A. A.; Abdelrady, Mohamed; Hassan, Mahdi; Nemr, Mohamed T. M.; Elshaier, Yaseen A.M.M.

doi:10.1039/d0ra05561a

Cited by 35 publications

(22 citation statements)

References 18 publications

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“…The synthesized derivatives displayed inhibitory activities toward both the COX-1 isozyme (IC 50 = 1.00–6.34 μM range) and the COX-2 isozyme (IC 50 = 0.09–0.71 μM range), with COX-2 selectivity indexes in the range of 3.03 to 16 in comparison with the COX-2 selective standard drug celecoxib (COX-1, IC 50 = 7.21 μM, COX-2, IC 50 = 0.83 μM and S.I. = 8.68) [ 73 ].…”

Section: Resultsmentioning

confidence: 99%

An Overview on Synthetic 2-Aminothiazole-Based Compounds Associated with Four Biological Activities

2021

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Amongst sulfur- and nitrogen-containing heterocyclic compounds, the 2-aminothiazole scaffold is one of the characteristic structures in drug development as this essential revelation has several biological activities abiding it to act as an anticancer, antioxidant, antimicrobial and anti-inflammatory agent, among other things. Additionally, various 2-aminothiazole-based derivatives as medical drugs have been broadly used to remedy different kinds of diseases with high therapeutic influence, which has led to their wide innovations. Owing to their wide scale of biological activities, their structural variations have produced attention amongst medicinal chemists. The present review highlights the recently synthesized 2-aminothiazole-containing compounds in the last thirteen years (2008–2020). The originality of this proposal is based on the synthetic strategies developed to access the novel 2-aminothiazole derivatives (N-substituted, 3-substituted, 4-substituted, multi-substituted, aryl/alkyl substituents or acyl/other substituents). The literature reports many synthetic pathways of these 2-aminothiazoles associated with four different biological activities (anticancer, antioxidant, antimicrobial and anti-inflammatory activities). It is wished that this review will be accommodating for new views in the expedition for rationalistic designs of 2-aminothiazole-based medical synthetic pathways.

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Section: Resultsmentioning

confidence: 99%

An Overview on Synthetic 2-Aminothiazole-Based Compounds Associated with Four Biological Activities

2021

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“…The peak identities were confirmed by the co-elution with the standards. All the assays were performed in duplicate [ 20 , 27 ].…”

Section: Methodsmentioning

confidence: 99%

“…K10542) for recording the blood pressure. The external jugular vein was also tightly cannulated for the administration of the tested compounds, followed by heparinized saline (0.90% ( w / v ) NaCl) [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

“…Conversely, the 2-aminothiazole-based heterocycles have attracted increased interest in the fields of drug design and discovery because of their effectiveness as small molecular drug candidates [ 8 , 9 ]. They are considered as a cornerstone for synthesizing many compounds with diverse pharmacological applications, such as anticancer [ 8 , 9 , 10 , 11 , 12 ], antibacterial [ 13 , 14 ], anti-inflammatory [ 15 , 16 , 17 ], antileishmanial [ 18 ], and influenza neuraminidase inhibitors [ 19 ], as well as PDE5 regulators and cyclooxygenases 1 and 2 (COX-1/COX-2) inhibitors [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Multifunctional Isosteric Pyridine Analogs-Based 2-Aminothiazole: Design, Synthesis, and Potential Phosphodiesterase-5 Inhibitory Activity

et al. 2021

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The elaboration of new small molecules that target phosphodiesterase enzymes (PDEs), especially those of type 5 (PDE5), is an interesting and emerging topic nowadays. A new series of heterocycle-based aminothiazoles were designed and synthesized from the key intermediate, 3-oxo-N-(thiazol-2-yl)butanamide (a PDE5 inhibitor that retains its amidic function), as an essential pharmacophoric moiety. The PDE5 inhibitors prevent the degradation of cyclic guanosine monophosphate, thereby causing severe hypotension as a marked side effect. Hence, an in vivo testing of the target compounds was conducted to verify its relation with arterial blood pressure. Utilizing sildenafil as the reference drug, Compounds 5, 10a, and 11b achieved 100% inhibitions of PDE5 without significantly lowering the mean arterial blood pressures (115.95 ± 2.91, 110.3 ± 2.84, and 78.3 ± 2.57, respectively). The molecular docking study revealed that the tested compounds exhibited docking poses that were similar to that of sildenafil (exploiting the amide functionality that interacted with GLN:817:A). The molecular shape and electrostatic similarity revealed a comparable physically achievable electrostatic potential with the reference drug, sildenafil. Therefore, these concomitant results revealed that the tested compounds exerted sildenafil-like inhibitory effects (although without its known drawbacks) on blood circulation, thus suggesting that the tested compounds might represent a cornerstone of beneficial drug candidates for the safe treatment for erectile dysfunction.

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“…3-Oxobutanamide are valuable intermediates in synthetic organic chemistry. Recently we reported a variety of synthesis of heteroaromatics that have been developed utilizing 3-oxobutanamides as readily obtainable compounds [11,12].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and antibacterial evaluation of some new pyrimidine, pyridine and thiophene derivatives

et al. 2021

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New series of pyrimidine, pyridine and thiophene derivatives were prepared by reaction of appropriate 3-oxobutanamides with urea, thiourea, active methylene compounds, arylidines, salicyaldehyde, chalcones, benzyl isothiocyanate and aminopyrazoles. Compounds 2a, 3a, 3c and 9 show activity against some bacterial species, whereas, no activity was observed for compounds 3b, 4, 5, 7e, 7f, 10 and 11 against all bacterial species (Graphical Abstract).

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Design, synthesis and biological evaluation of new 2-aminothiazole scaffolds as phosphodiesterase type 5 regulators and COX-1/COX-2 inhibitors

Abstract: A new series of 2-aminothiazole derivatives was designed and prepared as phosphodiesterase type 5 (PDE5) regulators and COX-1/COX-2 inhibitors.

Cited by 35 publications

References 18 publications

An Overview on Synthetic 2-Aminothiazole-Based Compounds Associated with Four Biological Activities

An Overview on Synthetic 2-Aminothiazole-Based Compounds Associated with Four Biological Activities

Multifunctional Isosteric Pyridine Analogs-Based 2-Aminothiazole: Design, Synthesis, and Potential Phosphodiesterase-5 Inhibitory Activity

Synthesis and antibacterial evaluation of some new pyrimidine, pyridine and thiophene derivatives

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