Evaluation of guanylhydrazone derivatives as inhibitors of Candida rugosa digestive lipase: Biological,biophysical, theoretical studies and biotechnological application |
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| Affiliation: | 1. Nursing and Pharmacy School, Federal University of Alagoas, Maceió, Brazil;2. Chemistry and Biotechnology Institute, Federal University of Alagoas, Maceió, Alagoas, Brazil;3. Laboratory of Cell Biochemistry, Federal University of São João del Rei, Dona Lindú Centro-Oeste Campus, Divinópolis, Minas Gerais, Brazil;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, P.O. Box 11829, Badr City, Cairo, Egypt;3. Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019 Sesto Fiorentino, Firenze, Italy;4. Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt;5. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia;6. Department of Applied Organic Chemistry, National Research Center, Dokki, Cairo 12622, Egypt;1. College of Plant Protection, Shenyang Agricultural University, Shenyang 110866, China;2. College of Science, China Agricultural University, Beijing 100091, China;1. University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh;2. Institut für Pharmakologie und Toxikologie, Universität Würzburg, Germany;1. Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, 10, Lavrentyev Ave., 630090 Novosibirsk, Russia;2. Novosibirsk Institute of Organic Chemistry of Siberian Branch of the Russian Academy of Sciences, 10, Lavrentyev Ave., 630090 Novosibirsk, Russia;3. Novosibirsk State University, 2, Pirogov Street, 630090 Novosibirsk, Russia;4. Federal Research Center of Fundamental and Translational Medicine of Siberian Branch of the Russian Academy of Sciences, 2, Timakov Street, 630117 Novosibirsk, Russia |
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| Abstract: | This work aimed to evaluate the inhibition of Candida rugosa lipase by five guanylhydrazone derivatives through biological, biophysical and theoretical studies simulating physiologic conditions. The compound LQM11 (IC50 = 14.70 μM) presented the highest inhibition against the enzyme. Therefore, for a better understanding of the interaction process, spectroscopic and theoretical studies were performed. Fluorescence and UV–vis assays indicate a static quenching mechanism with non-fluorescent supramolecular complex formation and changing the native protein structure. The binding process was spontaneous (ΔG < 0) and electrostatic forces (ΔH < 0 and ΔS > 0) played a preferential role in stabilizing the complex ligand-lipase. The compounds were classified as non-competitive inhibitors using orlistat as a reference in competition studies. Based on the 1H NMR assays it was possible to propose the sites of ligand (epitope) that bind preferentially to the enzyme and the theoretical studies were consistent with the experimental results. Finally, LQM11 was efficient as a lipase inhibitor of the crude intestinal extract of larvae of Rhynchophorus palmarum, an important agricultural plague, showing potential for control of this pest. Within this context, the real potential of this biotechnological application deserves further studies. |
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| Keywords: | Digestive lipase inhibitors Guanylhydrazone compounds Fluorescence interaction studies |
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