含有环烯的胺衍生物的设计,合成和抗菌活性
Dongdong Chen1, Yu Cheng2, Lele Shi2
1Department of Chemical and Material Engineering, Lyuliang University, Lvliang 033001, China.
Molecules (Basel, Switzerland)
|September 14, 2024
概括
合成了环胺衍生物,并测试了其抗菌特性. 三种化合物对Candida albicans表现出极好的抗真菌活性,具有作为新抗真菌剂的潜力.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 发现抗微生物药物 发现抗微生物药物
背景情况:
- 环是药物设计中的一个关键结构图案.
- 胺衍生物经常被探索其生物活性.
- 需要新的抗菌剂来对抗耐药性病原体.
研究的目的:
- 设计和合成新型环胺衍生物.
- 评估这些化合物的体外抗菌和抗真菌活性.
- 为了确定潜在的化合物用于抗真菌药物开发.
主要方法:
- 使用活性拼接合成53种环胺衍生物.
- 在体外对抗黄金葡萄球菌和大肠杆菌的抗菌活性进行了评估.
- 在体外评估抗真菌活性对Candida albicans.
- 针对CYP51蛋白点的分子对接研究.
主要成果:
- 合成了35种新型环胺衍生物.
- 几种化合物表现出适度的抗菌活性.
- 九种化合物对Candida albicans表现出抗真菌活性,其中三种化合物表现出极好的活性 (MIC80 = 16μg/mL).
- 化合物F8,F24和F42与CYP51蛋白具有良好的亲和力.
结论:
- 合成的环胺衍生物是抗真菌药物发现的一类有前途的化合物.
- 化合物F8,F24和F42是进一步开发作为针对CYP51.1的抗真菌剂的潜在候选者.
- 这项研究强调了环烯支架在开发新型抗微生物药物的实用性.
相关概念视频
Preparation of Amides
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Amides are synthesized by treating carboxylic acids with amines in the presence of dehydrating agents like dicyclohexylcarbodiimide (DCC).
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
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Nomenclature of Carboxylic Acid Derivatives: Amides and Nitriles
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Naming Amides
The IUPAC and common names of amides are derived from the parent carboxylic acid, by replacing the suffix “oic acid” and “ic acid,” respectively, with “amide.” In the following example, the IUPAC name ethanamide is derived from ethanoic acid, and the common name, acetamide, is obtained from acetic acid.
The IUPAC and common names of amides are derived from the parent carboxylic acid, by replacing the suffix “oic acid” and “ic acid,” respectively, with “amide.” In the following example, the IUPAC name ethanamide is derived from ethanoic acid, and the common name, acetamide, is obtained from acetic acid.
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Preparation of 1° Amines: Azide Synthesis
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Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
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Amines to Amides: Acylation of Amines
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Various carboxylic acid derivatives (such as acid chlorides, esters, and anhydrides) can be used for the acylation of amines to yield amides. The reaction requires two equivalents of amines. The first amine molecule functions as a nucleophile and attacks the carbonyl carbon to produce a tetrahedral intermediate. This is followed by the loss of the leaving group and restoration of the C=O bond.
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...
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Structures of Carboxylic Acid Derivatives
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Structure of Carboxylic Acid Derivatives
Carboxylic acid derivatives contain an acyl group attached to a heteroatom such as chlorine, oxygen, or nitrogen. The carbonyl carbon and oxygen are both sp2-hybridized with an unhybridized p orbital.
The three sp2 orbitals of the carbonyl carbon form three σ bonds, one each with the carbonyl oxygen, the α carbon, and the heteroatom, whereas the other two sp2 orbitals of the carbonyl oxygen are occupied by the lone pairs. Further, the...
Carboxylic acid derivatives contain an acyl group attached to a heteroatom such as chlorine, oxygen, or nitrogen. The carbonyl carbon and oxygen are both sp2-hybridized with an unhybridized p orbital.
The three sp2 orbitals of the carbonyl carbon form three σ bonds, one each with the carbonyl oxygen, the α carbon, and the heteroatom, whereas the other two sp2 orbitals of the carbonyl oxygen are occupied by the lone pairs. Further, the...
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Nomenclature of Aryl and Heterocyclic Amines
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The simplest aromatic amine is phenylamine, which contains an –NH2 functionality directly attached to an aromatic ring. The name aniline is designated for this skeleton. As shown in Figure 1, the common names of the functionalized anilines involve prefixes ortho-, meta-, and para- to indicate the substitution position. Different functionalized aniline derivatives also have notable trivial names.
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