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. 2015 Apr 20;16(4):8719-43.
doi: 10.3390/ijms16048719.

Synthesis, biological evaluation and 2D-QSAR study of halophenyl bis-hydrazones as antimicrobial and antitubercular agents

Hatem A Abdel-Aziz  1   2 , Wagdy M Eldehna  3 , Mohamed Fares  4 , Sara T A Al-Rashood  5 , Khalid A Al-Rashood  6 , Marwa M Abdel-Aziz  7 , Dalia H Soliman  8   9
Affiliations

Synthesis, biological evaluation and 2D-QSAR study of halophenyl bis-hydrazones as antimicrobial and antitubercular agents

Hatem A Abdel-Aziz et al. Int J Mol Sci. .

Abstract

In continuation of our endeavor towards the development of potent and effective antimicrobial agents, three series of halophenyl bis-hydrazones (14a-n, 16a-d, 17a and 17b) were synthesized and evaluated for their potential antibacterial, antifungal and antimycobacterial activities. These efforts led to the identification of five molecules 14c, 14g, 16b, 17a and 17b (MIC range from 0.12 to 7.81 μg/mL) with broad antimicrobial activity against Mycobacterium tuberculosis; Aspergillus fumigates; Gram positive bacteria, Staphylococcus aureus, Streptococcus pneumonia, and Bacillis subtilis; and Gram negative bacteria, Salmonella typhimurium, Klebsiella pneumonia, and Escherichia coli. Three of the most active compounds, 16b, 17a and 17b, were also devoid of apparent cytotoxicity to lung cancer cell line A549. Amphotericin B and ciprofloxacin were used as references for antifungal and antibacterial screening, while isoniazid and pyrazinamide were used as references for antimycobacterial activity. Furthermore, three Quantitative Structure Activity Relationship (QSAR) models were built to explore the structural requirements controlling the different activities of the prepared bis-hydrazones.

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Figures

Scheme 1
Scheme 1
Synthesis of compounds 14a–n. Reagents and conditions: i, MeOH/H2SO4/reflux 8 h; ii, NH2NH2.H2O/EtOH/reflux 4 h; iii, Neat, reflux 6 h; iv, MeOH/MeONa/reflux 8 h; v, HCl/NaNO2/H2O/0–5 °C; vi, CH3COONa/EtOH/0–5 °C; and vii, THF/reflux 10 h.
Scheme 2
Scheme 2
Synthesis of 16a–d and 17a,b. Reagents and conditions: i, EtOH/reflux 10 h; and ii, EtOH/reflux 15 h.
Figure 1
Figure 1
Predicted versus experimental pMIC of the tested compounds against Bacillis subtilis according to Equation (1) (r2 = 0.818).
Figure 2
Figure 2
Predicted versus experimental pMIC of the tested compounds against Klebsiella pneumonia according to Equation (2) (r2 = 0.785).
Figure 3
Figure 3
Predicted versus experimental pMIC of the tested compounds against Mycobacterium tuberculosis according to Equation (3) (r2 = 0.788).
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