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

• Published in: RSC advances Vol. 6; no. 29; pp. 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: Journal Article
• Language: English
• Published: 01.01.2016
• 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 sub( alpha )-NH sub( beta )-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 sub(3)O) sub(2)(S)P-NH sub( alpha )-NH sub( beta )-C(O)(C sub(4)H sub(4)O ) has more effect than the other compounds in inhibiting alpha -esterase. Docking analysis showed that hydrogen bonds were formed between the N-H sub( alpha ) protons of the (S)P-NH sub( alpha )-NH sub( beta )-C(S), (O)P-NH sub( alpha )-NH sub( beta )-C(S) and (O)P-NH sub( alpha )-NH sub( beta )-C(O) moieties with Gly323, Gly18 and Gly319 as well as the N-H sub( beta ) proton of the (S)P-NH sub( alpha )-NH sub( beta )-C(O) moiety and the AChE receptor site (Gly234). According to the QSAR model, the net charge of the N-H sub( alpha ) (Q sub(N( alpha ))) nitrogen atom contributes an important electronic function in the inhibition of AChE. A high interrelationship between Q sub(N( alpha )) and Q sub(P) proved that the NH-P(X) moiety has a higher inhibitory activity than the NH-C(X) moiety.