New Inhibition Detection Method to Evaluate the Human Salivary Alphaamylase Activity of Some Drugs, Molecular Docking, and SAR Studies.

BACKGROUND: For the first time, the investigation of six anti-inflammatory drugs and six antihistaminic drugs for inhibitory activities against alpha-amylase has been evaluated using a new inhibition detection method in order to find new treatments for some diseases caused by α-amylase. OBJECTIVE: The first part of this work was devoted to the evaluation of the inhibition activity of these drugs on salivary α-amylase in vitro. Then to study the nature of interactions and structure-activity relationship, using the Autodockvina program for molecular docking. MATERIALS AND METHODS: The evaluation of the inhibitory activity of our drugs is achieved using a new method that has proved its sensitivity, quickness, and effectiveness. RESULTS: The results of this study show that betamethasone and loratadine are potent α-amylase inhibitors with IC50 values 0.7mg/ml and 1.03 mg/ml, respectively compared to acarbose with IC50=5.6 µg/ml. CONCLUSION: The results showed that the loratadine and the betamethasone have a strong potential to inhibit the alpha-amylase.

In Silico and In Vitro Studies of the Inhibitory Effect of Antihistamine Drug Cyproheptadine Hydrochloride on Human Salivary Alpha Amylase.

BACKGROUND: For the first time, the inhibitory effects on the human salivary alpha-amylase activity of the anti-inflammatory drugs indomethacin, diclofenac sodium, ketoprofen, diclofenac potassium, diclofenac, triamcinolone acetonide, and the antihistamine drugs levocetirizine dihydrochloride, desloratadine, cycloheptadine hydrochloride, have been investigated to confirm the other properties of these drugs. OBJECTIVE: This study aimed to determine the effect of nine known drugs on human salivary α-amylase in vitro and the nature of interactions with structure-activity relationship using molecular docking experiments. METHODS: The inhibition of human salivary alpha amylase by the six anti-inflammatory and three antihistamine drugs has been carried out using the new method that has been proved in our previous work. Molecular docking has been achieved for the first time for these drugs using the Auto- Dock Vina program. RESULTS: Cyproheptadine hydrochloride presented the highest inhibitory activity against α-amylase with IC50=0.7 mg/ml, while the other drugs showed weak activities (IC50 > 2 mg/ml). CONCLUSION: We conclude that Cyproheptadine hydrochloride, which was studied by docking experiments, exhibited the best inhibitory activity on salivary α-amylase in vitro & in silico.

In silico and in vitro Study of the Inhibitory Effect of Antiinflammatory Drug Betamethasone on Two Lipases.

BACKGROUND: For the first time, the anti-inflammatory drug betamethasone is investigated for its inhibitory activity against lipase. OBJECTIVE: This work aims to demonstrate the in vitro and in silico inhibitory effect of the anti-inflammatory drug betamethasone on the enzymatic activity of two lipases. METHODS: In vitro study using p-nitrophenyllaurate as lipase substrate is used to determine inhibition potency. Molecular Docking is performed using the Autodock Vina for drug molecule and two enzymes Candida rugosa lipase and human pancreatic lipase. RESULTS: Betamethasone represents a moderate inhibition effect with a value of IC50 of 0.36±0.01 mg/ml. Molecular docking allowed us to understand inhibitory - enzyme interactions and to confirm in vitro obtained results. CONCLUSION: These experiments showed that betamethasone can be used in the treatment of diseases related to lipase activity.

Antiallergy Drugs as Potent Inhibitors of Lipase with Structure-activity Relationships and Molecular Docking.

BACKGROUND: Inhibition activity of 8 synthetic molecules known as anti-allergy drugs on lipases has been investigated. The enzymatic inhibition produced by these molecules is described here for the first time. OBJECTIVE: The used anti-allergy drugs are: Loratidine, primalan, zyrtec, histagan, periactin, ketotifene, rifex and bilastine. METHODS: Lipase inhibition is studied using the spectrophotometric method. Molecular docking has been achieved for the first time for these drugs using AutoDock Vina program to discuss the nature of interactions, structure-activity relationship and the mechanism of inhibition. RESULTS: The biological evaluation of these molecules showed that most of these drugs are potent lipase inhibitors with competitive type inhibition. The best drug is loratidine with IC50=0.44mg/ml and Ki=0.86 mM and competitive type inhibition. Molecular docking studies of the studied molecules confirmed their competitive inhibitory type with their binding to the Catalytic Active Site (CAS) of lipases. CONCLUSION: Hence, these drugs could be used for obesity or candidiasis treatment taking advantage of the much-known details of their secondary effects as antiallergy drugs.

Selection of orlistat as a potential inhibitor for lipase from Candida species.

Infections caused by Candida species manifest in a number of diseases, including candidemia, vulvovaginal candidiasis, endocarditis, and peritonitis. Candida species have been reported to possess lipolytic activity due to the secretion of lipolytic enzymes such as esterases, lipases and phospholipases. Extra-cellular hydrolytic enzymes seem to play an important role in Candida overgrowth. Candidiasis is commonly treated with antimycotics such as clotrimazole and nystatin. The antimycotics bind to a major component of the fungal cell membrane (ergosterol), forming pores that lead to death of the fungus. However, the secondary effects caused during such treatment have aroused a need to develop a treatment based on lipase inhibition. Nonetheless, no such lipase inhibitors for candidiasis treatment are currently available. Thus, we have performed a docking study with the natural inhibitor, orlistat or tetrahydrolipstatin. Our results have shown ten possible binding inhibitors to Candida rugosa lipase (CRL), out of which one possibility was selected, based on the weakest interatomic distance of 2.7 Å. Therefore, we propose the selection and design of a potential inhibitor candidate, orlistat for the treatment of candidiasis infections. However, this study has to be supported with in vitro and in vivo experiments to demonstrate the effectiveness of orlistat in lipase inhibition.