Abstract：
BACKGROUND: Piperine or piperic acid was isolated from fruits of Piper nigrum and had been reported as pharmacological valuable bioactive constituents. Keeping in view, a series of piperic acid-based N heterocyclic\'s derivatives were synthesized and evaluated for antibacterial activity. All these prepared ligands were docked to study the molecular interactions and binding affinities against the protein PDB ID: 5 CDP.
OBJECTIVE: To meet the real need of newer antibacterials, we designed and synthesized scaffolds with good antibacterial activity. The obtained antibacterials have been validated in terms of ligand-protein interaction and thus prove to build up as good drug candidates.
METHODS: Antibacterial activity of the compounds were carried out against bacterial strains; three Grampositive and three Gram-negative bacterial strains using agar well diffusion method. In silico molecular docking studies were carried out using Glide (grid-based ligand docking) program incorporated in the Schrödinger molecular modeling package by Maestro 11.0.
RESULTS: Compounds BC 28, BC 32, and BC 33 exhibits antibacterial activity along with Glide docking score of -8.580, -9.753 kcal/mol, and -8.813 kcal/mol, respectively. Docking studies explained hydrogen bonding, pi-pi, and hydrophobic interactions with amino acid residues which explain the binding affinity of the most docked ligand with protein.
CONCLUSIONS: In the present study, substituted piperic acid was synthesized and evaluated as antibacterial compared with standard drug ciprofloxacin and results interpret that having nitrogen as heteroatom in the heterocyclic nucleus found to be more potent than the standard drug ciprofloxacin. On comparing, substitution with electron-donating groups generates excellent antibacterial potential against the bacterial strains. It was also proved that having substitution with electron-donating groups on meta and para position with triazoline ring system exhibits greater potential while compounds which have a meta- electron-donating substituent showed lesser activity with thiazole nucleus. In addition, structure-based activities of the prepared analogs were discussed under Structure-Activity Relationship (SAR) section.
OBJECTIVE: To meet the real need of newer antibacterials, we designed and synthesized scaffolds with good antibacterial activity. The obtained antibacterials have been validated in terms of ligand-protein interaction and thus prove to build up as good drug candidates.
METHODS: Antibacterial activity of the compounds were carried out against bacterial strains; three Grampositive and three Gram-negative bacterial strains using agar well diffusion method. In silico molecular docking studies were carried out using Glide (grid-based ligand docking) program incorporated in the Schrödinger molecular modeling package by Maestro 11.0.
RESULTS: Compounds BC 28, BC 32, and BC 33 exhibits antibacterial activity along with Glide docking score of -8.580, -9.753 kcal/mol, and -8.813 kcal/mol, respectively. Docking studies explained hydrogen bonding, pi-pi, and hydrophobic interactions with amino acid residues which explain the binding affinity of the most docked ligand with protein.
CONCLUSIONS: In the present study, substituted piperic acid was synthesized and evaluated as antibacterial compared with standard drug ciprofloxacin and results interpret that having nitrogen as heteroatom in the heterocyclic nucleus found to be more potent than the standard drug ciprofloxacin. On comparing, substitution with electron-donating groups generates excellent antibacterial potential against the bacterial strains. It was also proved that having substitution with electron-donating groups on meta and para position with triazoline ring system exhibits greater potential while compounds which have a meta- electron-donating substituent showed lesser activity with thiazole nucleus. In addition, structure-based activities of the prepared analogs were discussed under Structure-Activity Relationship (SAR) section.
摘要：
背景：胡椒碱或胡椒酸是从黑胡椒的果实中分离出来的，并已被报道为药理学上有价值的生物活性成分。保持在视野中，合成了一系列基于胡椒酸的N杂环衍生物，并评估了其抗菌活性。将所有这些制备的配体对接以研究针对蛋白质PDBID:5CDP的分子相互作用和结合亲和力。
目的：为了满足新型抗菌药物的实际需求，我们设计并合成了具有良好抗菌活性的支架。所获得的抗菌剂已在配体-蛋白质相互作用方面进行了验证，因此证明可以作为良好的候选药物。
方法:使用琼脂孔扩散法对三种革兰氏阳性和三种革兰氏阴性细菌菌株进行化合物的抗菌活性。使用Maestro11.0纳入Schrödinger分子建模包中的Glide（基于网格的配体对接）程序进行了计算机分子对接研究。
结果：化合物BC28，BC32和BC33具有抗菌活性以及-8.580，-9.753kcal/mol的滑翔对接评分，和-8.813千卡/摩尔，分别。对接研究解释了氢键，pi-pi,以及与氨基酸残基的疏水相互作用，这解释了大多数对接配体与蛋白质的结合亲和力。
结论：在本研究中，与标准药物环丙沙星相比，合成了取代的哌啶酸并评估了其抗菌性，结果解释说，在杂环核中具有氮作为杂原子比标准药物环丙沙星更有效。在比较时，用给电子基团取代对细菌菌株产生优异的抗菌潜力。还证明,在间位和对位上具有三唑啉环系统的给电子基团的取代表现出更大的潜力,而具有给电子取代基的化合物对噻唑核的活性较低。此外,在结构-活性关系(SAR)部分讨论了制备的类似物的基于结构的活性。
目的：为了满足新型抗菌药物的实际需求，我们设计并合成了具有良好抗菌活性的支架。所获得的抗菌剂已在配体-蛋白质相互作用方面进行了验证，因此证明可以作为良好的候选药物。
方法:使用琼脂孔扩散法对三种革兰氏阳性和三种革兰氏阴性细菌菌株进行化合物的抗菌活性。使用Maestro11.0纳入Schrödinger分子建模包中的Glide（基于网格的配体对接）程序进行了计算机分子对接研究。
结果：化合物BC28，BC32和BC33具有抗菌活性以及-8.580，-9.753kcal/mol的滑翔对接评分，和-8.813千卡/摩尔，分别。对接研究解释了氢键，pi-pi,以及与氨基酸残基的疏水相互作用，这解释了大多数对接配体与蛋白质的结合亲和力。
结论：在本研究中，与标准药物环丙沙星相比，合成了取代的哌啶酸并评估了其抗菌性，结果解释说，在杂环核中具有氮作为杂原子比标准药物环丙沙星更有效。在比较时，用给电子基团取代对细菌菌株产生优异的抗菌潜力。还证明,在间位和对位上具有三唑啉环系统的给电子基团的取代表现出更大的潜力,而具有给电子取代基的化合物对噻唑核的活性较低。此外,在结构-活性关系(SAR)部分讨论了制备的类似物的基于结构的活性。
