New fluoroquinolones/nitric oxide donor hybrids: design, synthesis and antitubercular activity

被引：15

作者：

Aziz, Hossameldin A. ^{[1
]}

Moustafa, Gamal A. I. ^{[1
]}

Abbas, Samar H. ^{[1
]}

Hauk, Glenn ^{[2
]}

Krishna, Vagolu Siva ^{[3
]}

Sriram, Dharmarajan ^{[3
]}

Berger, James M. ^{[2
]}

Abuo-Rahma, Gamal El-Din A. ^{[1
]}

机构：

[1] Menia Univ, Fac Pharm, Dept Med Chem, Minia Minia 61519, Egypt

[2] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA

[3] Birla Inst Technol & Sci, Dept Pharm, Hyderabad Campus, Hyderabad, India

来源：

MEDICINAL CHEMISTRY RESEARCH | 2019年 / 28卷 / 08期

关键词：

Fluoroquinolones; Antitubercular; Nitric oxide (NO); Cleavable DNA complex; Molecular docking; NITRIC-OXIDE; DNA GYRASE; ANTIBACTERIAL; DERIVATIVES; COMPLEXES; MECHANISM; OXYGEN;

D O I：

10.1007/s00044-019-02372-y

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

New nitric oxide (NO) donating fluoroquinolones/nitrate ester hybrids were prepared and their structures were characterized by various spectroscopic and analytical tools. The release of NO from the prepared nitrate esters was measured using the modified Griess colorimetric method. Evaluation of antitubercular activity showed that most of tested compounds exhibited comparable or higher activity than the parent fluoroquinolones. Compounds 2b, 3a, 4a, 5a, and 2d showed better activity than ciprofloxacin. Nevertheless, none of the new compounds were superior to the parent fluoroquinolones in terms of DNA cleavage stimulation in mycobacteria. The additional growth inhibition effect that is distinct from gyrase poisoning may be due to release of NO or enhancement of lipophilicity. These data are augmented by docking results where the docked compounds did not exert additional significant bindings over the parent fluoroquinolones.

引用

页码：1272 / 1283

页数：12

共 43 条

[1] Novel N-4-piperazinyl-ciprofloxacin-chalcone hybrids: Synthesis, physicochemical properties, anticancer and topoisomerase I and II inhibitory activity [J].

Abdel-Aziz, Mohamed ;

Park, So-Eun ;

Abuo-Rahma, Gamal El-Din A. A. ;

Sayed, Mohamed A. ;

Kwon, Youngjoo .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2013, 69 :427-438

[2] New N-4 piperazinyl derivatives of norfloxacin: design, synthesis, and correlation of calculated physicochemical parameters with antibacterial activity [J].

Abuo-Rahma, Gamal El-Din ;

Abbas, Samar ;

Shoman, Mai ;

Samir, Ebtihal ;

Abdel-Baky, Rehab .

TURKISH JOURNAL OF CHEMISTRY, 2018, 42 (04) :1072-1085

[3] Design, synthesis, antibacterial activity and physicochemical parameters of novel N-4-piperazinyl derivatives of norfloxacin [J].

Abuo-Rahma, Gamal El-Din A. A. ;

Sarhan, Hatem. A. ;

Gad, Gamal F. M. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (11) :3879-3886

[4] New 1,2,4-triazole-Chalcone hybrids induce Caspase-3 dependent apoptosis in A549 human lung adenocarcinoma cells [J].

Ahmed, Fatma F. ;

Abd El-Hafeez, Amer Ali ;

Abbas, Samar H. ;

Abdelhamid, Dalia ;

Abdel-Aziz, Mohamed .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2018, 151 :705-722

[5] Mechanism of Quinolone Action and Resistance [J].

Aldred, Katie J. ;

Kerns, Robert J. ;

Osheroff, Neil .

BIOCHEMISTRY, 2014, 53 (10) :1565-1574

[6] Mycobacterium tuberculosis DNA gyrase:: Interaction with quinolones and correlation with antimycobacterial drug activity [J].

Aubry, A ;

Pan, XS ;

Fisher, LM ;

Jarlier, V ;

Cambau, E .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2004, 48 (04) :1281-1288

[7]

Aziz H.A., 2017, Eur J Chem, V8, P119, DOI [10.5155/eurjchem.8.2, DOI 10.5155/EURJCHEM.8.2.119-124.1549]

[8] TESTING POTENTIAL GYRASE INHIBITORS OF BACTERIAL-DNA GYRASE - A COMPARISON OF THE SUPERCOILING INHIBITION ASSAY AND CLEAVABLE COMPLEX ASSAY [J].

BARRETT, JF ;

BERNSTEIN, JI ;

KRAUSE, HM ;

HILLIARD, JJ ;

OHEMENG, KA .

ANALYTICAL BIOCHEMISTRY, 1993, 214 (01) :313-317

[9] Design, synthesis, nitric oxide release and antibacterial evaluation of novel nitrated ocotillol-type derivatives [J].

Bi, Yi ;

Yang, Xiao ;

Zhang, Tingting ;

Liu, Zeyun ;

Zhang, Xiaochen ;

Lu, Jing ;

Cheng, Keguang ;

Xu, Jinyi ;

Wang, Hongbo ;

Lv, Guangyao ;

Lewis, Peter John ;

Meng, Qingguo ;

Ma, Cong .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2015, 101 :71-80

[10] Crystal structure and stability of gyrase-fluoroquinolone cleaved complexes from Mycobacterium tuberculosis [J].

Blower, Tim R. ;

Williamson, Benjamin H. ;

Kerns, Robert J. ;

Berger, James M. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (07) :1706-1713

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