Ferrocene-bisphosphonates hybrid drug molecules: In vitro antibacterial and antifungal, in silico ADME, drug-likeness, and molecular docking studies
The design of hybrid molecules is a promising drug development strategy to prepare effective antimicrobial drugs that employ the concept of combination therapy. This strategy combines two therapeutic agents covalently to target different cellular pathways for synergistic effects. Ferrocene-bisphosph...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Results in Chemistry |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715623005179 |
| _version_ | 1797356323407396864 |
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| author | C.G. Anusionwu T.Y. Fonkui S.O. Oselusi S.A. Egieyeh B.A. Aderibigbe X.Y. Mbianda |
| author_facet | C.G. Anusionwu T.Y. Fonkui S.O. Oselusi S.A. Egieyeh B.A. Aderibigbe X.Y. Mbianda |
| author_sort | C.G. Anusionwu |
| collection | DOAJ |
| description | The design of hybrid molecules is a promising drug development strategy to prepare effective antimicrobial drugs that employ the concept of combination therapy. This strategy combines two therapeutic agents covalently to target different cellular pathways for synergistic effects. Ferrocene-bisphosphonate hybrid compounds, 1–8 were evaluated in vitro for their antibacterial and antifungal activities against selected fungal strains, gram-positive, and gram-negative bacteria. Hybrid compounds, 5, 6, and 8 exhibited significant antibacterial activity against all the bacterial strains than the control, fosfomycin with the lowest MIC value of ≤ 3 against Proteus mirabilis and Klebsiella aerogenes. The antifungal activity of hybrids, 2, 4, 5, and 6 against Penicillum Citrinum and Aspergillus ochraceus was high when compared to the control, nystatin. The lowest MIC values were 107 and 214 µM against Penicillum Citrinum and Aspergillus ochraceus for hybrid 5. The molecular docking studies revealed the inhibition of urease enzymes in Klebsiella aerogenes with a high binding energy of −3.973 and −4.645 Kcal/mol, respectively for hybrids 5 and 6. The in silico toxicity revealed the non-toxic effects of the hybrid compounds. The SwissADME parameters of the hybrid molecules further predicted good permeability, water solubility, and oral bioavailability, inability to cross the blood–brain barrier (BBB) and non-inhibition effects on some CYP isoenzymes, suggesting that their biotransformation will not be via the cytochrome isoenzymes. Most of the hybrids, 4–8 were predicted to be P-glycoprotein substrates. The hybrids obeyed Lipinski's rules with one violation, the Ghose rule, and the Egan rule. These findings indicate that the efficacy of hybrid compounds as promising antimicrobials and future studies are needed. |
| first_indexed | 2024-03-08T14:25:55Z |
| format | Article |
| id | doaj.art-36f76f7c241d4ec0a0b8f3d239833c8c |
| institution | Directory Open Access Journal |
| issn | 2211-7156 |
| language | English |
| last_indexed | 2024-03-08T14:25:55Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj.art-36f76f7c241d4ec0a0b8f3d239833c8c2024-01-13T04:44:09ZengElsevierResults in Chemistry2211-71562024-01-017101278Ferrocene-bisphosphonates hybrid drug molecules: In vitro antibacterial and antifungal, in silico ADME, drug-likeness, and molecular docking studiesC.G. Anusionwu0T.Y. Fonkui1S.O. Oselusi2S.A. Egieyeh3B.A. Aderibigbe4X.Y. Mbianda5Department of Chemical Sciences, University of Johannesburg, Doornfontein Campus, Johannesburg, South AfricaDepartment of Biotechnology, University of Johannesburg, Doornfontein Campus, Johannesburg, South AfricaSchool of Pharmacy, University of Western Cape, Bellville, Cape Town 7535, South AfricaSchool of Pharmacy, University of Western Cape, Bellville, Cape Town 7535, South AfricaDepartment of Chemistry, University of Fort Hare, Alice Campus, Eastern Cape, South Africa; Corresponding author.Department of Chemical Sciences, University of Johannesburg, Doornfontein Campus, Johannesburg, South AfricaThe design of hybrid molecules is a promising drug development strategy to prepare effective antimicrobial drugs that employ the concept of combination therapy. This strategy combines two therapeutic agents covalently to target different cellular pathways for synergistic effects. Ferrocene-bisphosphonate hybrid compounds, 1–8 were evaluated in vitro for their antibacterial and antifungal activities against selected fungal strains, gram-positive, and gram-negative bacteria. Hybrid compounds, 5, 6, and 8 exhibited significant antibacterial activity against all the bacterial strains than the control, fosfomycin with the lowest MIC value of ≤ 3 against Proteus mirabilis and Klebsiella aerogenes. The antifungal activity of hybrids, 2, 4, 5, and 6 against Penicillum Citrinum and Aspergillus ochraceus was high when compared to the control, nystatin. The lowest MIC values were 107 and 214 µM against Penicillum Citrinum and Aspergillus ochraceus for hybrid 5. The molecular docking studies revealed the inhibition of urease enzymes in Klebsiella aerogenes with a high binding energy of −3.973 and −4.645 Kcal/mol, respectively for hybrids 5 and 6. The in silico toxicity revealed the non-toxic effects of the hybrid compounds. The SwissADME parameters of the hybrid molecules further predicted good permeability, water solubility, and oral bioavailability, inability to cross the blood–brain barrier (BBB) and non-inhibition effects on some CYP isoenzymes, suggesting that their biotransformation will not be via the cytochrome isoenzymes. Most of the hybrids, 4–8 were predicted to be P-glycoprotein substrates. The hybrids obeyed Lipinski's rules with one violation, the Ghose rule, and the Egan rule. These findings indicate that the efficacy of hybrid compounds as promising antimicrobials and future studies are needed.http://www.sciencedirect.com/science/article/pii/S2211715623005179 |
| spellingShingle | C.G. Anusionwu T.Y. Fonkui S.O. Oselusi S.A. Egieyeh B.A. Aderibigbe X.Y. Mbianda Ferrocene-bisphosphonates hybrid drug molecules: In vitro antibacterial and antifungal, in silico ADME, drug-likeness, and molecular docking studies Results in Chemistry |
| title | Ferrocene-bisphosphonates hybrid drug molecules: In vitro antibacterial and antifungal, in silico ADME, drug-likeness, and molecular docking studies |
| title_full | Ferrocene-bisphosphonates hybrid drug molecules: In vitro antibacterial and antifungal, in silico ADME, drug-likeness, and molecular docking studies |
| title_fullStr | Ferrocene-bisphosphonates hybrid drug molecules: In vitro antibacterial and antifungal, in silico ADME, drug-likeness, and molecular docking studies |
| title_full_unstemmed | Ferrocene-bisphosphonates hybrid drug molecules: In vitro antibacterial and antifungal, in silico ADME, drug-likeness, and molecular docking studies |
| title_short | Ferrocene-bisphosphonates hybrid drug molecules: In vitro antibacterial and antifungal, in silico ADME, drug-likeness, and molecular docking studies |
| title_sort | ferrocene bisphosphonates hybrid drug molecules in vitro antibacterial and antifungal in silico adme drug likeness and molecular docking studies |
| url | http://www.sciencedirect.com/science/article/pii/S2211715623005179 |
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