Fused benzo[1,3]thiazine-1,2,3-triazole hybrids: Microwave-assisted one-pot synthesis, in vitro antibacterial, antibiofilm, and in silico ADME studies

Sucharitha, E. Ramya; Krishna, Thupurani Murali; Manchal, Ravinder; Gondru, Ramesh; Narsimha, Sirassu

doi:10.1016/j.bmcl.2021.128201

Cited by 38 publications

(22 citation statements)

References 28 publications

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“…Log P o/w values for conjugates were in compliance with the recommended range. Human intestinal absorption (HIA) : It was reported that the small intestine has a larger surface area and more permeable membranes than the stomach, and the majority of drugs orally administered solutions are largely absorbed through the small intestine [34] . The predicted percentages of HIA were calculated as 97.6 % for conjugate 7 and 100 % for all other conjugates which indicates that good intestinal absorption is to be expected [35] .…”

Section: Resultsmentioning

confidence: 99%

“…Human intestinal absorption (HIA): It was reported that the small intestine has a larger surface area and more permeable membranes than the stomach, and the majority of drugs orally administered solutions are largely absorbed through the small intestine. [34] The predicted percentages of HIA were calculated as 97.6 % for conjugate 7 and 100 % for all other conjugates which indicates that good intestinal absorption is to be expected. [35] Caco-2 permeability: The absorption of orally administered drugs in terms of Caco-2 permeability (recommended log Papp > 8 × 10 À 6 cm/s) was calculated in the range of 0.710 to 1.147.…”

Section: Structure Activity Relationship (Sar)mentioning

confidence: 92%

“…[33,38] The excretion of all conjugates was measured as total clearance (log value ml/min/kg) and renal OC2 substrate, and the conjugates were estimated to have negative clearance values and not renal OCT2 substrate. [33][34] The toxicity levels of the conjugates were estimated for AMES toxicity and hepatotoxicity. None of the conjugates were found to be toxic.…”

Section: Structure Activity Relationship (Sar)mentioning

confidence: 99%

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Steroid‐Hymecromone Conjugates with Improved Antiproliferative and Antimicrobial Potential: Synthesis, Biological Evaluation, and in silico ADME Prediction

Erdagi

2023

ChemistrySelect

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In this study, hymecromone with known therapeutic aspects was conjugated with steroids a class of natural products that widely exhibited broad biological functions. Cholic acid, diosgenin, cholesterol, DHEA, and testosterone were selected as steroid moiety, each of which has a different biological mechanism of action. This study focused on developing novel conjugates that can be used as multi‐targeted drugs for treating various diseases. All conjugates were evaluated in vitro for their antiproliferative and antimicrobial activities and discussed for the structure‐activity relationship. The conjugates 5 and 6 exhibited comparable cytotoxic effects to reference drugs against cancer cell lines (K562, MCF‐7, and HeLa) while showing no toxicity against healthy cells (L929). Conjugates 7 and 5 demonstrated antibacterial activity against Gram‐positive and Gram‐negative bacteria, with lower minimum inhibitory concentration (MIC) values than the standard ciprofloxacin drug. Conjugate 6, On the other hand, had the lowest MIC value against the fungus, comparable to that of the standard drug ketoconazole. The physicochemical and pharmacokinetic properties of conjugates were in silico computed and evaluated. Overall, the outputs of this study suggest that these conjugates have promising potential as therapeutic agents, offering a multi‐targeted approach for the treatment of various diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Structure Activity Relationship (Sar)mentioning

confidence: 92%

Section: Structure Activity Relationship (Sar)mentioning

confidence: 99%

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Steroid‐Hymecromone Conjugates with Improved Antiproliferative and Antimicrobial Potential: Synthesis, Biological Evaluation, and in silico ADME Prediction

Erdagi

2023

ChemistrySelect

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“…In this context, we have recently synthesized fused 1,2,3-triazoles using inexpensive Cu-catalyzed sequential 1,3-dipolar cycloaddition followed by intramolecular arylation. [15] Based on the all the above findings, inspired by the synthetic feasibility of 1,2,3-triazoles and in continuation of our group work on the development of fused 1,2,3-triazole based anticancer agents, [16] herein, we reported the CuI-catalyzed step-economical C-H arylation-based cascade synthesis of some new phenyl, morpholino and dioxidothiomorpholino containing [1,2,3]triazolo [5,1-a]isoquinolin-6(5H)-ones (Scheme 1) as EGFR directing in vitro cytotoxic agents. The EGFR is a cell-surface receptor, which shows a significant part in the ductal development of the mammary glands [17] and it's over-expression leads to a number of cancers.…”

Section: Introductionmentioning

confidence: 99%

“…However, these methods [13,14] require expensive palladium catalysts. In this context, we have recently synthesized fused 1,2,3‐triazoles using inexpensive Cu‐catalyzed sequential 1,3‐dipolar cycloaddition followed by intramolecular arylation [15] …”

Section: Introductionmentioning

confidence: 99%

Cu(I)‐Catalyzed One‐Pot Synthesis of [1,2,3]Triazolo[5,1‐a] isoquinolin‐6(5H)‐one Derivatives as EGFR‐Targeting Anticancer Agents

Samala¹,

Nukala²,

Thirukovela³

et al. 2022

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The CuI promoted one‐pot multi‐component synthesis of new fused [1,2,3]triazolo[5,1‐a]isoquinoline derivatives (4 a–4 h, 8 a–8 f & 9 a–9 f) without isolating unsafe azides and their in vitro cytotoxic activity against MCF‐7 & MDA‐MB‐231 (breast cancer cells) and A‐549 (alveolar carcinoma) was reported herein. Out of all, compounds 9‐chloro‐1‐(morpholinomethyl)‐[1,2,3]triazolo[5,1‐a]isoquinolin‐6(5H)‐one (8 d), 9‐fluoro‐1‐(morpholinomethyl)‐[1,2,3]triazolo[5,1‐a]isoquinolin‐6(5H)‐one (8 e), 9‐chloro‐1‐((1,1‐dioxidothiomorpholino)methyl)‐[1,2,3]triazolo[5,1‐a]isoquinolin‐6(5H)‐one (9 d), and 1‐((1,1‐dioxidothiomorpholino)methyl)‐9‐fluoro‐[1,2,3]triazolo[5,1‐a]isoquinolin‐6(5H)‐one (9 e) showed superior potency against all the cell lines than the standard drug erlotinib with IC50 values ranging from 2.45 to 7.19 μM. The most active compounds 8 d, 8 e, 9 d, and 9 e were also screened for their efficacy in inhibiting tyrosine kinase EGFR and results revealed that compound 9 d showed comparable activity with standard drug erlotinib, whereas, compounds 8 d, 8 e, and 9 e showed superior activity than the erlotinib. Molecular modeling studies for active compounds on EGFR (PDB‐ID‐4HJO) were also conducted and the obtained free energies were observed to be in agreement with the in vitro activity data. Finally, compounds 8 d, 8 e, 9 d, and 9 e didn't show AMES toxicity and followed the rules of Egan, Ghose, Veber, Lipinski, and Muegge rules without any deviation.

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Synthesis of novel [1,2,3]triazolo[4′,5′:3,4]pyrrolo[1,2‐a]thieno[2,3‐d] pyrimidines: Potent EGFR targeting anti‐breast cancer agents

Samala,

Bapuram

et al. 2024

Journal of Heterocyclic Chem

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In this study, we designed and synthesized several novel fused [1,2,3]triazolo [4′,5′:3,4]pyrrolo[1,2‐a]thieno[2,3‐d]pyrimidine derivatives using in a single [3 + 2] reaction cycloaddition reaction of 3‐(3‐iodoprop‐2‐yn‐1‐yl)thieno[2,3‐d]pyrimidin‐4(3H)‐one (4) followed by C‐C bond coupling with various aryl azides in a PEG‐400 medium. All of the newly synthesized compounds were evaluated in vitro for EGFR kinase inhibitory action as well as anti‐breast cancer activity against MDA‐MB‐231 and MCF‐7 breast cancer cell lines. When compared to the reference molecule, erlotinib, the majority of the compounds demonstrated adequate efficacy. The most promising compounds, 5g and 5i, demonstrated excellent anticancer activity against both cancer cell lines, with IC50 values ranging from 04.17 ± 0.55 to 8.65 ± 0.89 μM, respectively, as well as excellent kinase inhibitory activities (EGFR: IC50 = 0.467 ± 0.063 and 0.412 ± 0.081 μM). The in silico studies of five potent compounds 5f, 5g, 5h, 5i, and 5k were also carried out to identify the interactions against the EGFR receptor and found that the energy calculations were covenant with the obtained IC50 values.

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Fused benzo[1,3]thiazine-1,2,3-triazole hybrids: Microwave-assisted one-pot synthesis, in vitro antibacterial, antibiofilm, and in silico ADME studies

Cited by 38 publications

References 28 publications

Steroid‐Hymecromone Conjugates with Improved Antiproliferative and Antimicrobial Potential: Synthesis, Biological Evaluation, and in silico ADME Prediction

Steroid‐Hymecromone Conjugates with Improved Antiproliferative and Antimicrobial Potential: Synthesis, Biological Evaluation, and in silico ADME Prediction

Cu(I)‐Catalyzed One‐Pot Synthesis of [1,2,3]Triazolo[5,1‐a] isoquinolin‐6(5H)‐one Derivatives as EGFR‐Targeting Anticancer Agents

Synthesis of novel [1,2,3]triazolo[4′,5′:3,4]pyrrolo[1,2‐a]thieno[2,3‐d] pyrimidines: Potent EGFR targeting anti‐breast cancer agents

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