Synthesis of new urease enzyme inhibitors as antiulcer drug and computational study.

In search of potent urease inhibitor indole analogues (1-22) were synthesized and evaluated for their urease inhibitory potential. All analogues (1-22) showed a variable degree of inhibitory interaction potential having IC50 value ranging between 0.60 ± 0.05 to 30.90 ± 0.90 µM when compared with standard thiourea having IC50 value 21.86 ± 0.90 µM. Among the synthesized analogues, the compounds 1, 2, 3, 5, 6, 8, 12, 14, 18, 20 and 22 having IC50 value 3.10 ± 0.10, 1.20 ± 0.10, 4.60 ± 0.10, 0.60 ± 0.05, 5.30 ± 0.20, 2.50 ± 0.10, 7.50 ± 0.20, 3.90 ± 0.10, 3.90 ± 0.10, 2.30 ± 0.05 and 0.90 ± 0.05 µM respectively were found many fold better than the standard thiourea. All other analogues showed better urease interaction inhibition. Structure activity relationship (SAR) has been established for all analogues containing different substituents on the phenyl ring. To understand the binding interaction of most active analogues with enzyme active site docking study were performed.Communicated by Ramaswamy H. Sarma.

An effort to find new α-amylase inhibitors as potent antidiabetics compounds based on indole-based-thiadiazole analogs.

Inhibition of α-amylase enzyme is of key significance for the therapy of diabetes mellitus (DM). Numerous indole-based compounds have earlier been described for broad range of bioactivities. From our previous study, we knew that indole and thiadiazole are potent inhibitors of diabetics II. We design the hybrid molecules of them and synthesized 18 derivatives of indole-based-thiadiazole (1-18). All synthesized compounds were characterized using different spectroscopic methods and evaluated for their α-amylase inhibitory activities. All synthetic compounds, except 4, 13, 15 and 16, were found to be strongly active (IC50 values in the range of 0.80 ± 0.05 - 9.30 ± 0.20 µM) than the standard drug, acarbose (IC50 = 11.70 ± 0.10 µM). Nevertheless, compound 18 was found to be inactive. The modes of binding interactions of five most active compounds 2, 3, 5, 10 and 17 were also studies through molecular docking study. In brief, current study identifies a novel class of α-amylase inhibitors which can be further studied for the treatment of hyperglycemia and obesity.Communicated by Ramaswamy H. Sarma.

Synthesis of indole derivatives as diabetics II inhibitors and enzymatic kinetics study of α-glucosidase and α-amylase along with their in-silico study.

In this study, we have investigated a series of indole-based compounds for their inhibitory study against pancreatic α-amylase and intestinal α-glucosidase activity. Inhibitors of carbohydrate degrading enzymes appear to have an essential role as antidiabetic drugs. All analogous exhibited good to moderate α-amylase (IC50 = 3.80 to 47.50 µM), and α-glucosidase inhibitory interactions (IC50 = 3.10-52.20 µM) in comparison with standard acarbose (IC50 = 12.28 µM and 11.29 µM). The analogues 4, 11, 12, 15, 14 and 17 had good activity potential both for enzymes inhibitory interactions. Structure activity relationships were deliberated to propose the influence of substituents on the inhibitory potential of analogues. Docking studies revealed the interaction of more potential analogues and enzyme active site. Further, we studied their kinetic study of most active compounds showed that compounds 15, 14, 12, 17 and 11 are competitive for α-amylase and non- competitive for α-glucosidase.

Synthesis of indole-based-thiadiazole derivatives as a potent inhibitor of α-glucosidase enzyme along with in silico study.

A series of nineteen (1-19) indole-based-thiadiazole derivatives were synthesized, characterized by 1HNMR, 13C NMR, MS, and screened for α-glucosidase inhibition. All analogs showed varied α-glucosidase inhibitory potential with IC50 value ranged between 0.95 ± 0.05 to 13.60 ± 0.30 µM, when compared with the standard acarbose (IC50 = 1.70 ± 0.10). Analogs 17, 2, 1, 9, 7, 3, 15, 10, 16, and 14 with IC50 values 0.95 ± 0.05, 1.10 ± 0.10, 1.30 ± 0.10, 1.60 ± 0.10, 2.30 ± 0.10, 2.30 ± 0.10, 2.80 ± 0.10, 4.10 ± 0.20 and 4.80 ± 0.20 µM respectively showed highest α-glucosidase inhibition. All other analogs also exhibit excellent inhibitory potential. Structure activity relationships have been established for all compounds primarily based on substitution pattern on the phenyl ring. Through molecular docking study, binding interactions of the most active compounds were confirmed. We further studied the kinetics study of analogs 1, 2, 9 and 17 and found that they are Non-competitive inhibitors.

Exploring efficacy of indole-based dual inhibitors for α-glucosidase and α-amylase enzymes: In silico, biochemical and kinetic studies.

α-Glucosidase and α-amylase are enzymes which are associated with diabetic II. These enzymes break macromolecules of sugar into monosugar molecules which is soluble in body, hence increase the sugar level in blood. There is need to develop economical and save inhibitors to prevent them from breaking sugar macromolecules to soluble molecules which will control the level of sugar in blood. Therefore, we synthesized indole-based derivatives (1-18) and evaluated as dual inhibitor for α-glucosidase and α-amylase. These chemical scaffolds were built with variation in aryl ring which were found active with good to moderate activity for α-glucosidase having IC50 value ranging from 13.99 ± 0.10 to 59.09 ± 0.30 µM when compared with standard acarbose with IC50 of 11.29 ± 0.10 µM; for α-amylase IC50 value ranging from 13.14 ± 0.10 to 58.99 ± 0.30 µM when compared with the standard acarbose with IC50 of 11.12 ± 0.10 µM. Structure activity relationship (SAR) has been established for all compounds. Enzymatic kinetic study and molecular docking study have been carried out to investigate the binding interactions α-glucosidase and α-amylase enzyme.

Synthesis of indole based acetohydrazide analogs: Their in vitro and in silico thymidine phosphorylase studies.

In this study, a series of indole based acetohydrazide derivatives (1-22) were synthesized and characterized by 13C NMR, 1H NMR and HREI-MS. The resulted derivatives were tested for thymidine phosphorylase inhibitory potential. These derivatives inhibited thymidine phosphorylase at different concentration ranging from 1.10 ± 0.10 to 41.10 ± 1.10 µM when compared with the standard 7-Deazaxanthine (IC50 value 38.68 ± 1.12 µM). The compound 8 having OH group at 2, 4 and 6 position was found the most potent among the series with IC50 1.10 ± 0.10 µM. The structure activity relationships (SAR) has been established for all compounds keeping in the view the role of substitution and the effect of functional group which significantly affect thymidine phosphorylase activity. The nature of binding interactions of the most potent compounds and active sites of the enzymes was confirmed through molecular docking study.

Indole bearing thiadiazole analogs: synthesis, ß-glucuronidase inhibition and molecular docking study.

Indole based thiadiazole derivatives (1-22) have synthesized, characterized by NMR and HREI-MS and evaluated for ß-Glucuronidase inhibition. All compounds showed outstanding ß-glucuronidase activity with IC50 values ranging between 0.5 ± 0.08 to 38.9 ± 0.8 µM when compared with standard d-saccharic acid 1,4 lactone (IC50 value of 48.1 ± 1.2 µM). The compound 6, a 2,3-dihydroxy analog was found the most potent among the series with IC50 value 0.5 ± 0.08 µM. Structure activity relationship has been established for all compounds. To confirm the binding interactions of these newly synthesized compounds, molecular docking study have been carried out which reveal that these compounds established stronger hydrogen bonding networks with active site residues.

Synthesis, anti-leishmanial and molecular docking study of bis-indole derivatives.

We have synthesized new series of bisindole analogs (1-27), characterized by 1HNMR and HR-EI-MS and evaluated for their anti-leishmanial potential. All compounds showed outstanding inhibitory potential with IC50 values ranging from 0.7 ± 0.01 to 13.30 ± 0.50 µM respectively when compared with standard pentamidine with IC50 value of 7.20 ± 0.20 µM. All analogs showed greater potential than standard except 10, 19 and 23 when compared with standard. Structure activity relationship has been also established for all compounds. Molecular docking studies were carried out to understand the binding interaction of active molecules.

Synthesis, Molecular Docking and ß-Glucuronidase Inhibitory Potential of Indole Base Oxadiazole Derivatives.

ß-glucuronidase is a lysosomal glycosidase enzyme which catalyzes the extracellular matrix of cancer and normal cells and the glycosaminoglycans of the cell membrane, which is important for cancer cell proliferation, invasion, and metastasis. Liver cancer, colon carcinoma, and neoplasm bladder are triggered by the increase of the level of ß-glucuronidase activity. The most valuable structures are indole and oxadiazole which has gain immense attention because of its pharmacological behavior and display many biological properties. Twenty-two (1⁻22) analogs of indole based oxadiazole were synthesized and screened for their inhibitory potential against ß-glucuronidase. Majority of the compounds showed potent inhibitory potential with IC50 values ranging between 0.9 ± 0.01 to 46.4 ± 0.9 µM, under positive control of standard drug d-saccharic acid 1,4 lactone (IC50 = 48.1 ± 1.2 µM). Structural activity relationship (SAR) has been established for all synthesized compounds. To shed light on molecular interactions between the synthesized compounds and ß-glucuronidase, 1, 4, and 6 compounds were docked into the active binding site of ß-glucuronidase. The obtained results showed that this binding is thermodynamically favorable and ß-glucuronidase inhibition of the selected compounds increases with the number of hydrogen bonding established in selected compound-ß-glucuronidase complexes.

Synthesis of Thymidine Phosphorylase Inhibitor Based on Quinoxaline Derivatives and Their Molecular Docking Study.

We have synthesized quinoxaline analogs (1⁻25), characterized by ¹H-NMR and HREI-MS and evaluated for thymidine phosphorylase inhibition. Among the series, nineteen analogs showed better inhibition when compared with the standard inhibitor 7-Deazaxanthine (IC50 = 38.68 ± 4.42 µM). The most potent compound among the series is analog 25 with IC50 value 3.20 ± 0.10 µM. Sixteen analogs 1, 2, 3, 4, 5, 6, 7, 12, 13, 14, 15, 16, 17, 18, 21 and 24 showed outstanding inhibition which is many folds better than the standard 7-Deazaxanthine. Two analogs 8 and 9 showed moderate inhibition. A structure-activity relationship has been established mainly based upon the substitution pattern on the phenyl ring. The binding interactions of the active compounds were confirmed through molecular docking studies.

Synthesis and urease inhibitory potential of benzophenone sulfonamide hybrid in vitro and in silico.

This study deals with the synthesis of benzophenone sulfonamides hybrids (1-31) and screening against urease enzyme in vitro. Studies showed that several synthetic compounds were found to have good urease enzyme inhibitory activity. Compounds 1 (N'-((4'-hydroxyphenyl)(phenyl)methylene)-4''-nitrobenzenesulfonohydrazide), 2 (N'-((4'-hydroxyphenyl)(phenyl)methylene)-3''-nitrobenzenesulfonohydrazide), 3 (N'-((4'-hydroxyphenyl)(phenyl)methylene)-4''-methoxybenzenesulfonohydrazide), 4 (3'',5''-dichloro-2''-hydroxy-N'-((4'-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 6 (2'',4''-dichloro-N'-((4'-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 8 (5-(dimethylamino)-N'-((4-hydroxyphenyl)(phenyl)methylene)naphthalene-1-sulfono hydrazide), 10 (2''-chloro-N'-((4'-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 12 (N'-((4'-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide) have found to be potently active having an IC50 value in the range of 3.90-17.99 µM. These compounds showed superior activity than standard acetohydroxamic acid (IC50 = 29.20 ±â€¯1.01 µM). Moreover, in silico studies on most active compounds were also performed to understand the binding interaction of most active compounds with active sites of urease enzyme. Structures of all the synthetic compounds were elucidated by 1H NMR, 13C NMR, EI-MS and FAB-MS spectroscopic techniques.

Synthesis of benzothiazole derivatives as a potent α-glucosidase inhibitor.

Diabetes is one of the pre-dominant metabolic disorders all over the world. It is the prime reason of mortality and morbidity due to hyperglycemia which is link with numerus obstacles. Delaying absorption and digestion of carbohydrate has great therapeutic impact for governing postprandial hyperglycemia. Consequently, alpha glucosidase is one of the potential therapeutic approaches that reduce absorption of glucose and delay carbohydrate digestion hence maintaining blood glucose level. In this regard we have synthesized benzothiazole based oxadiazole in search of potent anti-diabetic agent as α-glucosidase Inhibitors. Benzothiazole based oxadiazole derivatives 1-23 have been synthesized, characterized by 1HNMR, 13CNMR, and MS and evaluated for α-glucosidase Inhibition. All analogs exhibited a varying degree of α-glucosidase inhibitory activity with IC50 values ranging in between 0.5 ±â€¯0.01-30.90 ±â€¯0.70 µM when compared with the standard acarbose (IC50 = 866.30 ±â€¯3.20 µM). Structure activity relationship has been established for all compounds. Molecular docking studies were performed to predict the binding interaction of the compounds with the active site of enzyme.

Synthesis of novel quinoline-based thiadiazole, evaluation of their antileishmanial potential and molecular docking studies.

New series of quinoline-based thiadiazole analogs (1-20) were synthesized, characterized by EI-MS, 1H NMR and 13C NMR. All synthesized compounds were subjected to their antileishmanial potential. Sixteen analogs 1-10, 12, 13, 16, 17, 18 and 19 with IC50 values in the range of 0.04 ±â€¯0.01 to 5.60 ±â€¯0.21 µM showed tremendously potent inhibition as compared to the standard pentamidine with IC50 value 7.02 ±â€¯0.09 µM. Analogs 11, 14, 15 and 20 with IC50 8.20 ±â€¯0.35, 9.20 ±â€¯0.40, 7.20 ±â€¯0.20 and 9.60 ±â€¯0.40 µM respectively showed good inhibition when compared with the standard. Structure-activity relationships have been also established for all compounds. Molecular docking studies were performed to determine the binding interaction of the compounds with the active site target.

Assessment of patient safety culture: a nationwide survey of community pharmacists in Kuwait.

BACKGROUND: Medication errors have been the largest component of medical errors threatening patient safety worldwide. Several international health bodies advocate measuring safety culture within healthcare organizations as an effective strategy for sustainable safety improvement. To the best of our knowledge, this is the first study conducted in a Middle Eastern country at the level of community pharmacy, to examine safety culture and to evaluate the extent to which patient safety is a strategic priority. METHODS: A descriptive cross-sectional study was conducted. The Pharmacy Survey on Patient Safety Culture (PSOPSC), developed by the Agency for Healthcare Research and Quality (AHRQ), was used to collect data. PSOPSC is a self-administered questionnaire which was previously tested for validity and reliability. The questionnaire was distributed among pharmacists who work in community pharmacies from the five governorates of Kuwait (Capital, Hawalli, Farwaniya, Jahra, and Ahmadi). The Statistical Package for Social Science (SPSS) software, version 24 was used for analysing data. RESULTS: A total of 255 community pharmacists from the five governorates were approached to participate in the study, of whom 253 returned a completed questionnaire, with the response rate of 99%. Results from the study showed that patient safety is a strategic priority in many aspects of patient safety standards at the level of community pharmacies. This was reflected by the high positive response rate (PRR) measures demonstrated in the domains of "Teamwork" (96.8%), "Organizational Learning-Continuous Improvement" (93.2%) and "Patient Counselling" (90.9%). On the other hand, the lowest PRR was given to the "Staffing, Work Pressure, and Pace" domain which scored 49.7%. CONCLUSIONS: Understanding community pharmacists' perspectives of patient safety culture within their organization is critical. It can help identify areas of strength and those that require improvement, which can help support decision about actions to improve patient safety. The current study showed that urgent attention should be given to the areas of weakness, mainly in the dimension of "Staffing, Work Pressure and Pace." The pharmacists pointed the need for adequate breaks between shifts and less distractible work environment to perform their jobs accurately.