Synthesis, toxicological and in silico evaluation of novel spiro pyrimidines against Culex pipiens L. referring to chitinase enzyme
The exponential development of resistance to conventional chemical insecticides adds another important motive for the creation of novel insecticidal active agents. One of the keys to meeting this challenge is the exploration of novel classes of insecticidal molecules with different modes of action....
Gespeichert in:
Veröffentlicht in: | Scientific reports 2024-01, Vol.14 (1), p.1516-1516, Article 1516 |
---|---|
Hauptverfasser: | , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | The exponential development of resistance to conventional chemical insecticides adds another important motive for the creation of novel insecticidal active agents. One of the keys to meeting this challenge is the exploration of novel classes of insecticidal molecules with different modes of action. Herein, a novel series of spiro pyrimidine derivatives was prepared using some green synthetic methodologies such as microwave irradiation, and sonication under ultrasound waves. Spiro pyrimidine aminonitrile
1
is a key starting material for the synthesis of targets
2–9
by reaction with different carbon electrophiles and nitrogen nucleophiles. The structures of all the newly synthesized compounds were approved using spectral data. The toxicological efficiency and biological impacts of the synthesized spiro pyrimidine derivatives were assessed against
Culex pipiens
L. larvae. The toxicity of synthesized compounds showed remarkable variations against the
C. pipiens
larvae. Where,
3
,
4
and
2
were the most efficient compounds with LC
50
values of 12.43, 16.29 and 21.73 µg/mL, respectively. While
1
was the least potent compound with an LC
50
value of 95.18 µg/mL. As well, other compounds were arranged according to LC
50
values as follows
5
>
7
>
6
>
9
>
8
. In addition,
3
and
4
exhibited significant prolongation of the developmental duration and greatly inhibited adult emergence. Moreover, many morphological deformities were observed in all developmental stages. Furthermore, cytotoxicity of the most effective compounds was assessed against the normal human cells (WI-38) as non-target organisms, where compounds
2
,
4
and
3
showed weak to non-toxic effects. The study of binding affinity and correlation between chemical structure and reactivity was carried out using molecular docking study and DFT calculations to investigate their mode of action. This study shed light on promising compounds with larvicidal activity and biological impacts on the
C. pipiens
life cycle. |
---|---|
ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-024-51771-8 |