Phosphorhydrazide inhibitors: toxicological profile and antimicrobial evaluation assay, molecular modeling and QSAR study

• Published in: RSC advances 2016-01, Vol.6 (29), p.24175-24189
• Main Authors: Gholivand, Khodayar, Asadi, Lida, Ebrahimi Valmoozi, Ali Asghar, Hodaii, Meraat, Sharifi, Mahboobeh, Kashani, Hadi Mazruee, Mahzouni, Hamid Reza, Ghadamyari, Mohammad, Kalate, Ali Asghar, Davari, Ehsan, Salehi, Sami, Bonsaii, Mahyar
• Format: Article
• Language: English
• Subjects: Antiinfectives and antibacterials; Bacteria; Charge; Chrysomelidae; Derivatives; Electronics; Insecticides; Molecular structure; Nitrogen atoms
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/c5ra24209f

A series of phosphorhydrazide (PHA) derivatives with the (X = O,S) P-NH α -NH β -C (X = O,S) skeleton ( 1-23 ) were synthesized and characterized by spectral techniques. A single crystal X-ray study of 4 and 21 provided confirmation of the hydrogen bonding structures. The synthesized compounds exhibited drastically reduced antibacterial activity against Gram-positive and -negative bacteria compared to the reference drugs. The insecticide activity of the PHAs appraised for the elm leaf beetle demonstrated that (CH 3 O) 2 (S)P-NH α -NH β -C(O)(C 4 H 4 O) has more effect than the other compounds in inhibiting α-esterase. Docking analysis showed that hydrogen bonds were formed between the N-H α protons of the (S)P-NH α -NH β -C(S), (O)P-NH α -NH β -C(S) and (O)P-NH α -NH β -C(O) moieties with Gly323, Gly18 and Gly319 as well as the N-H β proton of the (S)P-NH α -NH β -C(O) moiety and the AChE receptor site (Gly234). According to the QSAR model, the net charge of the N-H α ( Q N(α) ) nitrogen atom contributes an important electronic function in the inhibition of AChE. A high interrelationship between Q N(α) and Q P proved that the NH-P(X) moiety has a higher inhibitory activity than the NH-C(X) moiety. A series of 23 novel phosphorhydrazide derivatives were synthesized and characterized by spectral techniques, and their anti-ChE, antibacterial and insecticide activities were investigated.