Microwave produced 8-methyl-1,2,4,8-tetraazaspiro[4.5]dec-2-en-3-amine derivatives: their in vitro and in silico analysis

• Published in: Molecular diversity Vol. 28; no. 3; pp. 1409 - 1422
• Main Authors: Patel, Parth P., Patel, Navin B., Tople, Manesh S., Patel, Vatsal M., Ahmed, Iqrar, Patel, Harun
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-06-2024; Springer Nature B.V
• Subjects: Amines - chemistry; Amines - pharmacology; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Biochemistry; Biomedical and Life Sciences; Computer Simulation; Coronaviruses; DNA Gyrase - chemistry; DNA Gyrase - metabolism; E coli; Escherichia coli - drug effects; Hydrogen bonds; Life Sciences; Microbial Sensitivity Tests; Microwaves; Molecular Docking Simulation; Nitrogen; Organic Chemistry; Original; Original Article; Permeability; Pharmaceutical sciences; Pharmacy; Polymer Sciences; Spiro Compounds - chemical synthesis; Spiro Compounds - chemistry; Spiro Compounds - pharmacology; Tuberculosis; Antimicrobial; Microwave synthesis; ADME study; Antitubercular; Molecular docking
• ISSN: 1381-1991; 1573-501X
• DOI: 10.1007/s11030-023-10665-z

Compound
1
is formed by a microwave-assisted multicomponent reaction of 1-methylpiperidin-4-one, 2-amino-4-methoxy-6-methyl-1,3,5-triazine, and thiosemicarbazide, followed by the synthesis of Schiff base
2a–l
with a variety of aldehydes. A comparison was made between the conventional and microwave methods, and the microwave approach was shown to be considerably superior to the classical method since it takes less time and produces higher yields. Several spectral investigations, including
1
H NMR,
13
C NMR, Mass, and IR spectroscopy, are used to characterize the complete series. In vitro antibacterial testing suggests that compounds
2c
,
2f
, and
2g
are promising antibacterial agents, although compounds
2d
,
2e
, and
2l
are effective antimycobacterial agents when compared to the conventional medicine Rifampicin. The docking score from docking studies is considerable, which validates the results of the biological examination. Molecular docking was performed on
Escherichia coli DNA gyrase
. According to the in silico ADME analysis, each drug molecule is ideal for use in terms of drug solubility, hydrogen bonding, and cell permeability.
Graphical abstract