Molecular docking and antiviral activity of N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-2(4H)-yl)acetamides

Abstract

Two series of fifteen N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-2(4H)-yl)acetamides were screened for anti-HIV-1 activity and cytotoxicity. The compounds 6a, 6d, 6e, 6g and 6i from the series 6a-i of benzylamides and 7a, 7b, 7c, 7d and 7e from the series 7a-f of anilides were identified as effective anti-HIV-1 agents with EC50 values <20μM. Among these compounds that displayed anti-HIV-1 activity, 6a, 6e, 6g and 6i showed no toxicity in human PBM, CEM and Vero cells, with the exception of 6a which displayed toxicity in Vero cells. Molecular docking of these compounds provided insight into the molecular mechanism and it was found that 6e, 6g and 6i bound deeply in the NNRTI binding pocket of the HIV-1 reverse transcriptase, using RT-bound nevirapine X-ray data and molecular docking for validation, showing the potential of these new structures as inhibitors of this viral enzyme.

Discovery of Novel HCV NS5B polymerase inhibitor, 2‐(3,4‐dimethyl‐5,5‐dioxidobenzo[e]pyrazolo[4,3‐c][1,2]thiazin‐2(4H)‐yl)‐N‐(2‐fluorobenzyl)acetamide via molecular docking and experimental approach

“…The future directive to the study is utilising undruggable chaperon blockage that intervenes folding mechanisms could serve as an approach for the development of novel drugs via targeting undruggable proteins. 19 To summarise, 6c has remarkable anti-NS5B activity and sound docking potential to NS5B binding sites. Therefore, the synthetic compound reported in this study could be a milestone for new antiviral discovery targeting viral polymerases.…”

“…For instance, many of its derivatives have been explored as anti-human immunodeficiency virus (HIV) agents. [18][19][20] Furthermore, several others have reported being effective as an anti-HCV NS5B agents. [21][22][23] All these aspects supported NS5B evaluation as a potential target for antiviral inhibitors.…”

N -Arylacetamide derivatives of methyl 1,2-benzothiazine-3-carboxylate as potential drug candidates for urease inhibition

“…They are well-known non-steroidal anti-inflammatory drugs (NSAIDs) commercially available as oxicams [ 29 ]. Studies reveal that 1,2-benzothiazines exhibit wide pharmacological activities such as anti-inflammatory [ 30 ], calpain I inhibitors [ 31 ], anti-cancer [ 32 ], anti-microbial [ 33 ], analgesic [ 34 ], MAPK inhibitors [ 35 ], MAO inhibition [ 36 ], anti-arthritic [ 37 ], anti-oxidant [ 38 ], anti-viral [ 39 , 40 ], anti-diabetic [ 41 ], anti-convulsant [ 42 ] and anti-malarial [ 43 ]. Other applications include as herbicides and as dyestuff in industry [ 44 ].…”

Design, Synthesis, and in vitro Evaluation of Tubulin‐Targeting Dibenzothiazines with Antiproliferative Activity as a Novel Heterocycle Building Block

“…On to other hand, the skeleton of the dibenzothiazines is constituted by the 1,2 benzothiazine 1,1-dioxide building block, which presents a wide variety of biological activities, including antihepatitis C virus (HCV), [39,40] 11β-HSD1 inhibitors, [41,42] anti-HIV and anticancer. [43,44] The aim of this work is the design and synthesis of several (di)benzothiazine derivatives to explore these scaffolds as building blocks of potentially biological active compounds. The biological activity was evaluated against a panel of human tumor cell lines using the SRB antiproliferative/cytotoxicity assay, [45][46][47] as well as in vitro to determine their cellular target.…”