Статья

5-Benzyliden-2-(5-methylthiazol-2-ylimino)thiazolidin-4-ones as Antimicrobial Agents. Design, Synthesis, Biological Evaluation and Molecular Docking Studies

M. Haroun, C. Tratrat, A. Kolokotroni, A. Petrou, A. Geronikaki, M. Ivanov, M. Kostic, M. Sokovic, A. Carazo, P. Mladěnka, N. Sreeharsha, K. Venugopala, A. Nair, H. Elsewedy,
2021

In this study, we report the design, synthesis, computational and experimental evaluation of the antimicrobial activity, as well as docking studies of new 5-methylthiazole based thiazolidinones. All compounds demonstrated antibacterial efficacy, some of which (1, 4, 10 and 13) exhibited good activity against E. coli and B. cereus. The evaluation of antibacterial activity against three resistant strains, MRSA, P. aeruginosa and E. coli, revealed that compound 12 showed the best activity, higher than reference drugs ampicillin and streptomycin, which were inactive or exhibited only bacteriostatic activity against MRSA, respectively. Ten out of fifteen compounds demonstrated higher potency than reference drugs against a resistant strain of E. coli, which appeared to be the most sensitive species to our compounds. Compounds 8, 13 and 14 applied in a concentration equal to MIC reduced P. aeruginosa biofilm formation by more than 50%. All compounds displayed antifungal activity, with compound 10 being the most active. The majority of compounds showed better activity than ketoconazole against almost all fungal strains. In order to elucidate the mechanism of antibacterial and antifungal activities, molecular docking studies on E. coli Mur B and C. albicans CYP51 and dihydrofolate reductase were performed. Docking analysis of E. coli MurB indicated a probable involvement of MurB inhibition in the antibacterial mechanism of tested compounds while docking to 14α-lanosterol demethylase (CYP51) and tetrahydrofolate reductase of Candida albicans suggested that probable involvement of inhibition of CYP51 reductase in the antifungal activity of the compounds. Potential toxicity toward human cells is also reported.

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  • 1. Version of Record от 2021-03-17

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Об авторах
  • M. Haroun
    Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia;, christophetratrat@gmail.com, (C.T.);, sharsha@kfu.edu.sa, (N.S.);, kvenugopala@kfu.edu.sa, (K.N.V.);, anair@kfu.edu.sa, (A.B.N.);, helsewedy@kfu.edu.sa, (H.S.E.)
  • C. Tratrat
    Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia;, christophetratrat@gmail.com, (C.T.);, sharsha@kfu.edu.sa, (N.S.);, kvenugopala@kfu.edu.sa, (K.N.V.);, anair@kfu.edu.sa, (A.B.N.);, helsewedy@kfu.edu.sa, (H.S.E.)
  • A. Kolokotroni
    School of Health, Department of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;, aggelikikolokotroni@gmail.com, (A.K.);, anthi.petrou.thessaloniki1@gmail.com, (A.P.)
  • A. Petrou
    School of Health, Department of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;, aggelikikolokotroni@gmail.com, (A.K.);, anthi.petrou.thessaloniki1@gmail.com, (A.P.)
  • A. Geronikaki
    School of Health, Department of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;, aggelikikolokotroni@gmail.com, (A.K.);, anthi.petrou.thessaloniki1@gmail.com, (A.P.)
  • M. Ivanov
    Mycological Laboratory, Department of Plant Physiology, Institute for Biological Research, Siniša Stanković-National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11000 Belgrade, Serbia;, marija.smiljkovic@ibiss.bg.ac.rs, (M.I.);, marina.kostic@ibiss.bg.ac.rs, (M.K.);, mris@ibiss.bg.ac.rs, (M.S.)
  • M. Kostic
    Mycological Laboratory, Department of Plant Physiology, Institute for Biological Research, Siniša Stanković-National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11000 Belgrade, Serbia;, marija.smiljkovic@ibiss.bg.ac.rs, (M.I.);, marina.kostic@ibiss.bg.ac.rs, (M.K.);, mris@ibiss.bg.ac.rs, (M.S.)
  • M. Sokovic
    Mycological Laboratory, Department of Plant Physiology, Institute for Biological Research, Siniša Stanković-National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11000 Belgrade, Serbia;, marija.smiljkovic@ibiss.bg.ac.rs, (M.I.);, marina.kostic@ibiss.bg.ac.rs, (M.K.);, mris@ibiss.bg.ac.rs, (M.S.)
  • A. Carazo
    Department of pharmacology and toxicology, Faculty of Pharmacy, Charles University, 500 05 Hradec Králové, Czech Republic;, carazofa@faf.cuni.cz, (A.C.);, mladenkap@faf.cuni.cz, (P.M.)
  • P. Mladěnka
    Department of pharmacology and toxicology, Faculty of Pharmacy, Charles University, 500 05 Hradec Králové, Czech Republic;, carazofa@faf.cuni.cz, (A.C.);, mladenkap@faf.cuni.cz, (P.M.)
  • N. Sreeharsha
    Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia;, christophetratrat@gmail.com, (C.T.);, sharsha@kfu.edu.sa, (N.S.);, kvenugopala@kfu.edu.sa, (K.N.V.);, anair@kfu.edu.sa, (A.B.N.);, helsewedy@kfu.edu.sa, (H.S.E.)
  • K. Venugopala
    Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia;, christophetratrat@gmail.com, (C.T.);, sharsha@kfu.edu.sa, (N.S.);, kvenugopala@kfu.edu.sa, (K.N.V.);, anair@kfu.edu.sa, (A.B.N.);, helsewedy@kfu.edu.sa, (H.S.E.), Department of Biotechnology and Food Technology, Faculty of Applied Sciences, Durban University of Technology, Durban 4001, South Africa
  • A. Nair
    Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia;, christophetratrat@gmail.com, (C.T.);, sharsha@kfu.edu.sa, (N.S.);, kvenugopala@kfu.edu.sa, (K.N.V.);, anair@kfu.edu.sa, (A.B.N.);, helsewedy@kfu.edu.sa, (H.S.E.)
  • H. Elsewedy
    Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia;, christophetratrat@gmail.com, (C.T.);, sharsha@kfu.edu.sa, (N.S.);, kvenugopala@kfu.edu.sa, (K.N.V.);, anair@kfu.edu.sa, (A.B.N.);, helsewedy@kfu.edu.sa, (H.S.E.)
Название журнала
  • Antibiotics
Том
  • 10
Выпуск
  • 3
Страницы
  • 309
Издатель
  • MDPI
Тип документа
  • journal article
Тип лицензии Creative Commons
  • CC BY
Правовой статус документа
  • Свободная лицензия
Источник
  • dimensions