Anti-HIV activity of new pyrazolobenzothiazine 5,5-dioxide-based acetohydrazides

Khalid, Zunera; Aslam, Sana; Ahmad, Matloob; Munawar, Munawar Ali; Montero, Catherine; Detorio, Mervi; Parvez, Masood; Schinazi, Raymond F.

doi:10.1007/s00044-015-1411-z

Cited by 14 publications

(3 citation statements)

References 35 publications

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“…These compounds have anti-bacterial, anti-inflammatory, antioxidant activity (Kumar et al 2012). During our previous work, we have identified benzothiazine derivatives as antiviral agents (Aslam et al 2014a;Khalid et al 2015), cholinesterase (Aslam et al 2014b) and monoamine oxidase inhibitors (Abid et al 2017;Ahmad et al 2019). The present study is designed to investigate the In-silico and in-vitro anti-diabetic activity of pyrazolobenzothiazine 5,5 dioxide derivatives to minimize the blood glucose level as well as diabetic complications.…”

Section: Introductionmentioning

confidence: 99%

Alpha-glucosidase activity of novel pyrazolobenzothiazine 5,5-dioxide derivatives for the treatment of diabetes mellitus. Invitro combined with molecular docking approach

et al. 2019

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Diabetes mellitus is a metabolic disease caused due to the improper secretion of insulin which leads to hyperglycaemia. According to the International Diabetes Federation (IDF), 371 million people are affected by diabetes worldwide, while 7 million people are suffering from this disease in Pakistan. Pyrazolobenzothiazine 5,5-dioxide derivatives have anti-bacterial, anti-inflammatory, antioxidant activity and have the potential to treat diabetes and other diseases. This study was designed to perform in-silico and in-vitro analysis of pyrazolobenzothiazine 5,5-dioxide derivatives against αglucosidase for the treatment of diabetes mellitus. For this purpose, pyrazolobenzothiazine 5,5-dioxide derivatives were synthesized in the laboratory. Molecular docking analysis of pyrazolobenzothiazine 5,5-dioxide derivatives against αglucosidase was achieved through Molecular Operating Environment (MOE) and ranked them based on binding affinity. Compounds with strong binding interaction were selected for invitro anti-diabetic analysis by enzyme inhibition assay against αglucosidase using p-nitrophenyl-α-Dglucopyranoside (PNPG) as a substrate. Furthermore, the dose-response analysis was performed via Microdilution method. Compounds having strong bonding interactions with the active site and high scores were selected for in-vitro analysis. Compounds 1a, 1f, 1 g, 1 h showed strong bonding interaction with the active site of αglucosidase and have docking score − 11.303, −10.189, −10.360, −10.160 respectively. Compound 1e, 1f, 1 g and 1 h showed IC50 at the concentration of 4.7 μM, 8.8 μM, 12.2 μM and 11.2 μM respectively in ezyme inhibition assay. The outcome of this study proved helpful to determine new antidiabetic agents to minimize diabetes complication.

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Section: Introductionmentioning

confidence: 99%

Alpha-glucosidase activity of novel pyrazolobenzothiazine 5,5-dioxide derivatives for the treatment of diabetes mellitus. Invitro combined with molecular docking approach

et al. 2019

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“…Furthermore, the 1,2-benzothiazine-3-carbohydrazides 6 and 7 (Figure 1) were proven good α-glucosidase inhibitors, with IC 50 values of 3.9 and 4.2 µM, respectively [29,30]. Some other biological activities shown by 1,2-benzothiazine derivatives are MAO inhibitors [31], α-glucosidase inhibitors [32,33], anti-inflammatory agents [34], antiviral agents [35][36][37][38], anticancer agents [39,40], antitumor agents [41], cholinesterase inhibitors [42] and anti-microbial agents [43]. In addition, various sulfonamides were also found to be good inhibitors of α-glucosidase [44] and α-amylase [45] enzymes.…”

Section: Introductionmentioning

confidence: 99%

Identification of Cyclic Sulfonamides with an N-Arylacetamide Group as α-Glucosidase and α-Amylase Inhibitors: Biological Evaluation and Molecular Modeling

et al. 2022

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Diabetes mellitus (DM), a complicated metabolic disorder, is due to insensitivity to insulin function or reduction in insulin secretion, which results in postprandial hyperglycemia. α-Glucosidase inhibitors (AGIs) and α-amylase inhibitors (AAIs) block the function of digestive enzymes, which delays the carbohydrate hydrolysis process and ultimately helps to control the postprandial hyperglycemia. Diversified 2-(3-(3-methoxybenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-N-arylacetamides were synthesized and evaluated for their in vitro inhibitory potential against α-glucosidase and α-amylase enzymes. The compounds with chloro, bromo and methyl substituents demonstrated good inhibition of α-glucosidase enzymes having IC50 values in the range of 25.88–46.25 μM, which are less than the standard drug, acarbose (IC50 = 58.8 μM). Similarly, some derivatives having chloro, bromo and nitro substituents were observed potent inhibitors of α-amylase enzyme, with IC50 values of 7.52 to 15.06 μM, lower than acarbose (IC50 = 17.0 μM). In addition, the most potent compound, N-(4-bromophenyl)-2-(4-hydroxy-3-(3-methoxybenzoyl)-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)acetamide (12i), was found to be a non-competitive and competitive inhibitor of α-glucosidase and α-amylase enzymes, respectively, during kinetic studies. The molecular docking studies provided the binding modes of active compounds and the molecular dynamics simulation studies of compound 12i in complex with α-amylase also showed that the compound is binding in a fashion similar to that predicted by molecular docking studies.

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“…Among the approved by FDA compounds are several heterocyclic compounds such as benzoxazin-2-one (etravirine), dipirydo [1,4] diazepine-6-one (etravirin) [4], piperazine and indolyl (delaverdine) moieties [5,6]. Except of these drugs many other molecules have been found to display RT inhibitory action [7,8,9,10,11,12,13], among which are: benzothiazine dioxides [14], N1,N3-disubstituted uracils [15], 6-arylmethyl-substituted S-DABOs [16], adamantyl-substituted thiazolidine-4-ones [17,18] and many others [19,20,21,22,23,24,25,26,27]. The 2,3-diaryl-thiazolidin-4-one scaffold appeared as a selective NNRTI [28,29].…”

Section: Introductionmentioning

confidence: 99%

Novel Thiazolidin-4-ones as Potential Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase

et al. 2019

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Background: HIV is the causative agent of Acquired Immunodeficiency Syndrome (AIDS), an infectious disease with increasing incidence worldwide. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) play an important role in the treatment of AIDS. Although, many compounds are already being used as anti-HIV drugs, research for the development of new inhibitors continues as the virus develops resistant strains. Methods: The best features of available NNRTIs were taken into account for the design of novel inhibitors. PASS (Prediction of activity spectra for substances) prediction program and molecular docking studies for the selection of designed compounds were used for the synthesis. Compounds were synthesized using conventional and microwave irradiation methods and HIV RT inhibitory action was evaluated by colorimetric photometric immunoassay. Results: The evaluation of HIV-1 RT inhibitory activity revealed that seven compounds have significantly lower ΙC50 values than nevirapine (0.3 μΜ). It was observed that the activity of compounds depends not only on the nature of substituent and it position in benzothiazole ring but also on the nature and position of substituents in benzene ring. Conclusion: Twenty four of the tested compounds exhibited inhibitory action lower than 4 μΜ. Seven of them showed better activity than nevirapine, while three of the compounds exhibited IC50 values lower than 5 nM. Two compounds 9 and 10 exhibited very good inhibitory activity with IC50 1 nM.

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Anti-HIV activity of new pyrazolobenzothiazine 5,5-dioxide-based acetohydrazides

Cited by 14 publications

References 35 publications

Alpha-glucosidase activity of novel pyrazolobenzothiazine 5,5-dioxide derivatives for the treatment of diabetes mellitus. Invitro combined with molecular docking approach

Alpha-glucosidase activity of novel pyrazolobenzothiazine 5,5-dioxide derivatives for the treatment of diabetes mellitus. Invitro combined with molecular docking approach

Identification of Cyclic Sulfonamides with an N-Arylacetamide Group as α-Glucosidase and α-Amylase Inhibitors: Biological Evaluation and Molecular Modeling

Novel Thiazolidin-4-ones as Potential Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase

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