AUTHOR=Kundu Riya , Shakil Najam Akhtar , Narayanan Neethu , Kamil Deeba , Rana Virendra Singh , Tripathi Kailash P. , Kaushik Parshant 

TITLE=Novel indazolylchromones: synthesis, fungicidal evaluation, molecular docking and aquatic toxicity prediction

JOURNAL=Frontiers in Chemistry

VOLUME=12

YEAR=2024

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2024.1411187

DOI=10.3389/fchem.2024.1411187

ISSN=2296-2646

ABSTRACT=<p>Fungal diseases cause substantial loss to agricultural crops, affecting both quantities and quality. Although several methods are used for preventing disease incidence, fungicides remain crucial for higher yields and better quality. But in the past, the efficacy of several fungicides has decreased due to increased cases of fungicide resistant. In our pursuit of new effective fungicides, we synthesised a series of twenty 2-Indazol-1-yl-chromen-4-one derivatives (6a- 6t). The characterization of synthesized compounds was performed by several spectroscopic methods including Infrared, Nuclear Magnetic Resonance (<sup>1</sup>H and <sup>13</sup>C) and HRMS. Out of 20 synthesised compounds, 19 (6b- 6t) were found to be novel. All synthesised indazolylchromones showed very good antifungal activity against <italic>Sclerotium rolfsii</italic> and <italic>Fusarium oxysporum</italic>. Among the tested compounds, <bold>6t</bold> and <bold>6f</bold> exhibited very good fungicidal activity against <italic>S. rolfsii</italic> with an ED<sub>50</sub> of 10.10 mg L<sup>-1</sup> and 16.18 mg L<sup>-1</sup>, respectively. In case of <italic>Fusarium oxysporum</italic> compound <bold>6f</bold> displayed good’ activity with an ED<sub>50</sub> value of 27.82 mg L<sup>-1</sup>. Molecular docking study was done to predict the binding sites of most active compounds, <bold>6t</bold> and <bold>6f</bold> with Cytochrome P450 14alpha -sterol demethylase (CYP51) enzyme using molsoft software. The acute toxicity predictions the of synthesized compounds for fish (LC<sub>50</sub>,96 Hr), daphnid (LC<sub>50</sub>, 48 Hr) and green algae (EC<sub>50</sub>, 96Hr) and the chronic toxicity predictions (ChV) were assessed using Ecological Structure Activity Relationship (ECOSAR) model. As per ECOSAR prediction, all the chemicals are inside AD and not missing predictions.</p>