4-(Indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole Acylamines as Νovel Antimicrobial Agents: Synthesis, In Silico and In Vitro Evaluation
This manuscript deals with the synthesis and computational and experimental evaluation of the antimicrobial activity of twenty-nine 4-(indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole acylamines. An evaluation of antibacterial activity against Gram (+) and Gram (−) bacteria revealed that the M...
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2021
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oai:doaj.org-article:1bae1751f15a47b794a3fea7fe68d3d52021-11-25T18:39:18Z4-(Indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole Acylamines as Νovel Antimicrobial Agents: Synthesis, In Silico and In Vitro Evaluation10.3390/ph141110961424-8247https://doaj.org/article/1bae1751f15a47b794a3fea7fe68d3d52021-10-01T00:00:00Zhttps://www.mdpi.com/1424-8247/14/11/1096https://doaj.org/toc/1424-8247This manuscript deals with the synthesis and computational and experimental evaluation of the antimicrobial activity of twenty-nine 4-(indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole acylamines. An evaluation of antibacterial activity against Gram (+) and Gram (−) bacteria revealed that the MIC of indole derivatives is in the range of 0.06–1.88 mg/mL, while among fourteen methylindole derivatives, only six were active, with an MIC in the range of of 0.47–1.88 mg/mL. <i>S. aureus</i> appeared to be the most resistant strain, while <i>S.</i> Typhimurium was the most sensitive. Compound <b>5x</b> was the most promising, with an MIC in the range of 0.06–0.12 mg/mL, followed by <b>5d</b> and <b>5m</b>. An evaluation of these three compounds against resistant strains, namely MRSA <i>P.</i> <i>aeruginosa</i> and <i>E.</i> <i>coli</i>, revealed that they were more potent against MRSA than ampicillin. Furthermore, compounds <b>5m</b> and <b>5x</b> were superior inhibitors of biofilm formation, compared to ampicillin and streptomycin, in terms Compounds <b>5d</b>, <b>5m</b>, and <b>5x</b> interact with streptomycin in additive manner. The antifungal activity of some compounds exceeded or was equipotent to those of the reference antifungal agents bifonazole and ketoconazole. The most potent antifungal agent was found to be compound <b>5g</b>. Drug likeness scores of compounds was in a range of −0.63 to 0.29, which is moderate to good. According to docking studies, <i>E. coli</i> MurB inhibition is probably responsible for the antibacterial activity of compounds, whereas CYP51 inhibition was implicated in antifungal activity. Compounds appeared to be non-toxic, according to the cytotoxicity assessment in MRC-5 cells.Sergei SimakovVictor KartsevAnthi PetrouIoannis NicolaouAthina GeronikakiMarija IvanovMarina KosticJasmina GlamočlijaMarina SokovićDespoina TaleaIoannis S. VizirianakisMDPI AGarticle4-(indol-3-yl)thiazole-2-amines4-ιndol-3-yl)thiazole acylaminesantimicrobialantifungaldockingMedicineRPharmacy and materia medicaRS1-441ENPharmaceuticals, Vol 14, Iss 1096, p 1096 (2021) |
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| topic |
4-(indol-3-yl)thiazole-2-amines 4-ιndol-3-yl)thiazole acylamines antimicrobial antifungal docking Medicine R Pharmacy and materia medica RS1-441 |
| spellingShingle |
4-(indol-3-yl)thiazole-2-amines 4-ιndol-3-yl)thiazole acylamines antimicrobial antifungal docking Medicine R Pharmacy and materia medica RS1-441 Sergei Simakov Victor Kartsev Anthi Petrou Ioannis Nicolaou Athina Geronikaki Marija Ivanov Marina Kostic Jasmina Glamočlija Marina Soković Despoina Talea Ioannis S. Vizirianakis 4-(Indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole Acylamines as Νovel Antimicrobial Agents: Synthesis, In Silico and In Vitro Evaluation |
| description |
This manuscript deals with the synthesis and computational and experimental evaluation of the antimicrobial activity of twenty-nine 4-(indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole acylamines. An evaluation of antibacterial activity against Gram (+) and Gram (−) bacteria revealed that the MIC of indole derivatives is in the range of 0.06–1.88 mg/mL, while among fourteen methylindole derivatives, only six were active, with an MIC in the range of of 0.47–1.88 mg/mL. <i>S. aureus</i> appeared to be the most resistant strain, while <i>S.</i> Typhimurium was the most sensitive. Compound <b>5x</b> was the most promising, with an MIC in the range of 0.06–0.12 mg/mL, followed by <b>5d</b> and <b>5m</b>. An evaluation of these three compounds against resistant strains, namely MRSA <i>P.</i> <i>aeruginosa</i> and <i>E.</i> <i>coli</i>, revealed that they were more potent against MRSA than ampicillin. Furthermore, compounds <b>5m</b> and <b>5x</b> were superior inhibitors of biofilm formation, compared to ampicillin and streptomycin, in terms Compounds <b>5d</b>, <b>5m</b>, and <b>5x</b> interact with streptomycin in additive manner. The antifungal activity of some compounds exceeded or was equipotent to those of the reference antifungal agents bifonazole and ketoconazole. The most potent antifungal agent was found to be compound <b>5g</b>. Drug likeness scores of compounds was in a range of −0.63 to 0.29, which is moderate to good. According to docking studies, <i>E. coli</i> MurB inhibition is probably responsible for the antibacterial activity of compounds, whereas CYP51 inhibition was implicated in antifungal activity. Compounds appeared to be non-toxic, according to the cytotoxicity assessment in MRC-5 cells. |
| format |
article |
| author |
Sergei Simakov Victor Kartsev Anthi Petrou Ioannis Nicolaou Athina Geronikaki Marija Ivanov Marina Kostic Jasmina Glamočlija Marina Soković Despoina Talea Ioannis S. Vizirianakis |
| author_facet |
Sergei Simakov Victor Kartsev Anthi Petrou Ioannis Nicolaou Athina Geronikaki Marija Ivanov Marina Kostic Jasmina Glamočlija Marina Soković Despoina Talea Ioannis S. Vizirianakis |
| author_sort |
Sergei Simakov |
| title |
4-(Indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole Acylamines as Νovel Antimicrobial Agents: Synthesis, In Silico and In Vitro Evaluation |
| title_short |
4-(Indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole Acylamines as Νovel Antimicrobial Agents: Synthesis, In Silico and In Vitro Evaluation |
| title_full |
4-(Indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole Acylamines as Νovel Antimicrobial Agents: Synthesis, In Silico and In Vitro Evaluation |
| title_fullStr |
4-(Indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole Acylamines as Νovel Antimicrobial Agents: Synthesis, In Silico and In Vitro Evaluation |
| title_full_unstemmed |
4-(Indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole Acylamines as Νovel Antimicrobial Agents: Synthesis, In Silico and In Vitro Evaluation |
| title_sort |
4-(indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole acylamines as νovel antimicrobial agents: synthesis, in silico and in vitro evaluation |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/1bae1751f15a47b794a3fea7fe68d3d5 |
| work_keys_str_mv |
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| _version_ |
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