Exploring Acyl Thiotriazinoindole Based Pharmacophores: Design, Synthesis, and SAR Studies with Molecular Docking and Biological Activity Profiling against Urease, α-amylase, α-glucosidase, Antimicrobial, and Antioxidant Targets

A diminutive chemical library of acyl thiotriazinoindole (ATTI) based bioactive scaffolds was synthesized, instigated by taking the economical starting material Isatin, through a series of five steps. Isatin was first nitrated followed by the attachment of pentyl moiety via nucleophilic substitution...

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Published in:PROTEIN JOURNAL
Main Authors: Haider, Mian Bilal; Saeed, Aamer; Ahmed, Atteeque; Azeem, Muhammad; Ismail, Hammad; Mehmood, Sabba; Taslimi, Parham; Shah, Syed Adnan Ali; Irfan, Madiha; El-Seedi, Hesham R.
Format: Article
Language:English
Published: SPRINGER 2024
Subjects:
Online Access:https://www-webofscience-com.uitm.idm.oclc.org/wos/woscc/full-record/WOS:001303880000001
author Haider
Mian Bilal; Saeed
Aamer; Ahmed
Atteeque; Azeem
Muhammad; Ismail
Hammad; Mehmood
Sabba; Taslimi
Parham; Shah
Syed Adnan Ali; Irfan
Madiha; El-Seedi
Hesham R.
spellingShingle Haider
Mian Bilal; Saeed
Aamer; Ahmed
Atteeque; Azeem
Muhammad; Ismail
Hammad; Mehmood
Sabba; Taslimi
Parham; Shah
Syed Adnan Ali; Irfan
Madiha; El-Seedi
Hesham R.
Exploring Acyl Thiotriazinoindole Based Pharmacophores: Design, Synthesis, and SAR Studies with Molecular Docking and Biological Activity Profiling against Urease, α-amylase, α-glucosidase, Antimicrobial, and Antioxidant Targets
Biochemistry & Molecular Biology
author_facet Haider
Mian Bilal; Saeed
Aamer; Ahmed
Atteeque; Azeem
Muhammad; Ismail
Hammad; Mehmood
Sabba; Taslimi
Parham; Shah
Syed Adnan Ali; Irfan
Madiha; El-Seedi
Hesham R.
author_sort Haider
spelling Haider, Mian Bilal; Saeed, Aamer; Ahmed, Atteeque; Azeem, Muhammad; Ismail, Hammad; Mehmood, Sabba; Taslimi, Parham; Shah, Syed Adnan Ali; Irfan, Madiha; El-Seedi, Hesham R.
Exploring Acyl Thiotriazinoindole Based Pharmacophores: Design, Synthesis, and SAR Studies with Molecular Docking and Biological Activity Profiling against Urease, α-amylase, α-glucosidase, Antimicrobial, and Antioxidant Targets
PROTEIN JOURNAL
English
Article
A diminutive chemical library of acyl thiotriazinoindole (ATTI) based bioactive scaffolds was synthesized, instigated by taking the economical starting material Isatin, through a series of five steps. Isatin was first nitrated followed by the attachment of pentyl moiety via nucleophilic substitution reaction. The obtained compound was reacted with thiosemicarbazide to obtain thiosemicarbazone derivative, which was eventually cyclized using basic conditions in water as solvent. Finally, the reported series was obtained through reaction of nitrated thiotriazinoindole moiety with differently substituted phenacyl bromides. The synthesized compounds were characterized using NMR spectroscopy and elemental analysis. Finally, the synthesized motifs were scrutinized for their potential to impede urease, alpha-glucosidase, DPPH, and alpha-amylase. Compound 5 h with para cyano group manifested the most pivotal biological activity among all, displaying IC50 values of 29.7 +/- 0.8, 20.5 +/- 0.5 and 36.8 +/- 3.9 mu M against urease, alpha-glucosidase, and DPPH assay, respectively. Simultaneously, for alpha-amylase compound 5 g possessing a p-CH3 at phenyl ring unfolded as most active, with calculated IC50 values 90.3 +/- 1.1 mu M. The scaffolds were additionally gauged for their antifungal and antibacterial activity. Among the tested strains, 5d having bromo as substituent exhibited the most potent antibacterial activity, while it also demonstrated the highest potency against Aspergillus fumigatus. Other derivatives 5b, 5e, 5i, and 5j also exhibited dual inhibition against both antibacterial and antifungal strains. The interaction pattern of derivatives clearly displayed their SAR, and their docking scores were correlated with their IC50 values. In molecular docking studies, the importance of interactions like hydrogen bonding was further asserted. The electronic factors of various substituents engendered variety of interactions between the ligands and targets implying their importance in the structures of the synthesized heterocyclic scaffolds. To conclude, the synthesized compounds had satisfactory biological activity against various important targets. Further studies are therefore encouraged by attachment of different substitutions in the structure at various positions to enhance the activity of these compounds.
SPRINGER
1572-3887
1875-8355
2024
43
5
10.1007/s10930-024-10229-6
Biochemistry & Molecular Biology

WOS:001303880000001
https://www-webofscience-com.uitm.idm.oclc.org/wos/woscc/full-record/WOS:001303880000001
title Exploring Acyl Thiotriazinoindole Based Pharmacophores: Design, Synthesis, and SAR Studies with Molecular Docking and Biological Activity Profiling against Urease, α-amylase, α-glucosidase, Antimicrobial, and Antioxidant Targets
title_short Exploring Acyl Thiotriazinoindole Based Pharmacophores: Design, Synthesis, and SAR Studies with Molecular Docking and Biological Activity Profiling against Urease, α-amylase, α-glucosidase, Antimicrobial, and Antioxidant Targets
title_full Exploring Acyl Thiotriazinoindole Based Pharmacophores: Design, Synthesis, and SAR Studies with Molecular Docking and Biological Activity Profiling against Urease, α-amylase, α-glucosidase, Antimicrobial, and Antioxidant Targets
title_fullStr Exploring Acyl Thiotriazinoindole Based Pharmacophores: Design, Synthesis, and SAR Studies with Molecular Docking and Biological Activity Profiling against Urease, α-amylase, α-glucosidase, Antimicrobial, and Antioxidant Targets
title_full_unstemmed Exploring Acyl Thiotriazinoindole Based Pharmacophores: Design, Synthesis, and SAR Studies with Molecular Docking and Biological Activity Profiling against Urease, α-amylase, α-glucosidase, Antimicrobial, and Antioxidant Targets
title_sort Exploring Acyl Thiotriazinoindole Based Pharmacophores: Design, Synthesis, and SAR Studies with Molecular Docking and Biological Activity Profiling against Urease, α-amylase, α-glucosidase, Antimicrobial, and Antioxidant Targets
container_title PROTEIN JOURNAL
language English
format Article
description A diminutive chemical library of acyl thiotriazinoindole (ATTI) based bioactive scaffolds was synthesized, instigated by taking the economical starting material Isatin, through a series of five steps. Isatin was first nitrated followed by the attachment of pentyl moiety via nucleophilic substitution reaction. The obtained compound was reacted with thiosemicarbazide to obtain thiosemicarbazone derivative, which was eventually cyclized using basic conditions in water as solvent. Finally, the reported series was obtained through reaction of nitrated thiotriazinoindole moiety with differently substituted phenacyl bromides. The synthesized compounds were characterized using NMR spectroscopy and elemental analysis. Finally, the synthesized motifs were scrutinized for their potential to impede urease, alpha-glucosidase, DPPH, and alpha-amylase. Compound 5 h with para cyano group manifested the most pivotal biological activity among all, displaying IC50 values of 29.7 +/- 0.8, 20.5 +/- 0.5 and 36.8 +/- 3.9 mu M against urease, alpha-glucosidase, and DPPH assay, respectively. Simultaneously, for alpha-amylase compound 5 g possessing a p-CH3 at phenyl ring unfolded as most active, with calculated IC50 values 90.3 +/- 1.1 mu M. The scaffolds were additionally gauged for their antifungal and antibacterial activity. Among the tested strains, 5d having bromo as substituent exhibited the most potent antibacterial activity, while it also demonstrated the highest potency against Aspergillus fumigatus. Other derivatives 5b, 5e, 5i, and 5j also exhibited dual inhibition against both antibacterial and antifungal strains. The interaction pattern of derivatives clearly displayed their SAR, and their docking scores were correlated with their IC50 values. In molecular docking studies, the importance of interactions like hydrogen bonding was further asserted. The electronic factors of various substituents engendered variety of interactions between the ligands and targets implying their importance in the structures of the synthesized heterocyclic scaffolds. To conclude, the synthesized compounds had satisfactory biological activity against various important targets. Further studies are therefore encouraged by attachment of different substitutions in the structure at various positions to enhance the activity of these compounds.
publisher SPRINGER
issn 1572-3887
1875-8355
publishDate 2024
container_volume 43
container_issue 5
doi_str_mv 10.1007/s10930-024-10229-6
topic Biochemistry & Molecular Biology
topic_facet Biochemistry & Molecular Biology
accesstype
id WOS:001303880000001
url https://www-webofscience-com.uitm.idm.oclc.org/wos/woscc/full-record/WOS:001303880000001
record_format wos
collection Web of Science (WoS)
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