Synthesis, Biological Evaluation, and QSAR Studies of 3-Iodochromone Derivatives as Potential Fungicides.

Parshant Kaushik,Virendra S Rana,Najam A Shakil

doi:10.3389/fchem.2021.636882

Abstract

Despite the emergence of novel biotechnological and biological solutions, agrochemicals continue to play an important role in crop protection. Fungicide resistance is becoming a major problem; numerous cases of fungicide resistance have occurred worldwide in the last decade, resulting in the loss of several fungicides. The discovery of new molecules has therefore assumed critical importance in crop protection. In our quest for biologically active molecules, we herein report the synthesis of a series of twenty-one 3-Iodochromone derivatives (4a–4u), in a two-step process by condensation of 2-hydroxyacetophenone derivatives (2a–2u) with N,N-dimethylformamidedimethylacetal yielding enaminones (3a–3u), followed by cyclization with iodine to corresponding 3-iodochromones. Characterization of these compounds was done by IR, 1H NMR, 13C NMR, and LC-HRMS techniques. All synthesized compounds were screened for their fungicidal activity against Sclerotium rolfsii. Among these 6,8-Dichloro-3-iodochromone 4r was found to be most active (ED50 = 8.43 mg L−1). 2D-Quantitative Structural Activity Relationship (2D-QSAR) analysis was also performed by generating three different models viz., Multiple Linear Regression (MLR, Model 1), Principal Component Regression (PCR, Model 2), and Partial Least Squares (PLS, Model 3). Predictive power and statistical significance of these models were assessed with external and internal validation and leave one-out cross-validation was used for verification. In QSAR study, MLR (Model 1) was found to be best having correlation coefficient (r2) 0.943, cross-validated correlation coefficient (q2) 0.911 and r2pred 0.837. It was observed that DeltaEpsilonC, T_2_Cl_6, T_2_F_6, T_T_F_3, and ZCompDipole are the major descriptors which influence the fungicidal activity of 3-Iodochromone derivatives. The physicochemical parameters were estimated by the VLifeMDS 4.6 software. The QSAR study results will be helpful for structure optimization to improve the activity.

Highlights

The growth of human civilization has been closely related to crop production, and plant diseases have been a concern for human being perhaps since plants were cultivated more than 10,000 years ago
The study revealed that all test compounds showed fungicidal activity against S. rolfsii., but compound 4r showed the highest activity
The variables in developed model equations established that structural, molecular shape analysis, electronic, and thermodynamic descriptors played a major role in fungicidal activity of the compounds

Summary

INTRODUCTION

The growth of human civilization has been closely related to crop production, and plant diseases have been a concern for human being perhaps since plants were cultivated more than 10,000 years ago. The major mass fragments observed were C21H33O3+(333), C7H5O3+(137), C5H8NO+(98), and C4H10N+(72) It was obtained as bright yellow solid in 87% yield; m.p.: 128–132°C, Rf: 0.50 (ethyl acetate: hexane, 3:7). The major mass fragments observed were C7H3Cl2O2+(188), C5H8NO+(98), and C4H10N+(72) It was obtained as bright yellow solid in 84% yield; m.p.: 105–109°C, Rf: 0.52 (ethyl acetate: hexane, 3:7). The major mass fragments observed were C21H33O3+(333), C7H4FO2+(139), C6H4FO+(111), C5H8NO+(98), and C4H10N+(72) It was obtained as bright yellow solid in 80% yield; m.p.: 131–135°C, Rf: 0.49 (ethyl acetate: hexane, 3:7). The magnitude of different descriptors employed for developing QSAR models were present in contribution charts (Figure 2)

AND DISCUSSION

CONCLUSION