Novel heterocyclic 1,3,4-oxadiazole derivatives of fluoroquinolones as a potent antibacterial agent: Synthesis and computational molecular modeling

Allaka, Tejeswara Rao; Kummari, Bhaskar; Polkam, Naveen; Naveen, Kanagaraj; Chepuri, Kalyani; Anireddy, Jaya Shree

doi:10.1007/s11030-021-10287-3

Cited by 28 publications

(15 citation statements)

References 39 publications

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“…They can be introduced into C-3 via the formation of different functional derivatives of carboxylic acids that are presented in Scheme 1 . For instance, alkylation offers an opportunity to further obtain hydrazine derivatives [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. The carboxylic group can be easily turned into an amide group with the subsequent formation of nitriles [ 56 ].…”

Section: Introductionmentioning

confidence: 99%

“…As for further cyclization, literature data present investigations that describe synthesized 3-heteroaryl hybrids of fluoroquinolones with oxadiazole [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 57 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ], isoxadiazole [ 55 , 68 ], triazole [ 25 , 26 , 30 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 65 , 71 , 72 , 73 , 74 , 75 ], thiadiazole [ 25 , 26 , 47 , 59 , 60 , 71 , 75 , 76 , 77 ,…”

Section: Introductionmentioning

confidence: 99%

“…One of the leading positions among them is given to the oxadiazole ring that was used for modification of fluoroquinolones of the second (norfloxacin, ciprofloxacin, ofloxacin, pefloxacin) and third (levofloxacin, enrofloxacin) generations [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 57 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ]. The main routes for the introduction of the oxadiazole ring into C-3 of fluoroquinolones are depicted in Scheme 2 .…”

Section: Introductionmentioning

confidence: 99%

“…Thus, such modifications include: alkylation of the thiol group in oxadiazol [ 27 , 30 , 31 , 36 , 48 ] or s-triazol [ 30 , 36 , 41 , 60 ] moieties; condensation with aromatic aldehydes for amino derivatives [ 45 , 71 , 77 , 82 ]; and Mannich reaction [ 45 ] with formaldehyde and amines.…”

Section: Introductionmentioning

confidence: 99%

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A Comprehensive Review on Chemical Synthesis and Chemotherapeutic Potential of 3-Heteroaryl Fluoroquinolone Hybrids

et al. 2023

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Fluoroquinolones have been studied for more than half a century. Since the 1960s, four generations of these synthetic antibiotics have been created and successfully introduced into clinical practice. However, they are still of interest for medicinal chemistry due to the wide possibilities for chemical modification, with subsequent useful changes in the pharmacokinetics and pharmacodynamics of the initial molecules. This review summarizes the chemical and pharmacological results of fluoroquinolones hybridization by introducing different heterocyclic moieties into position 3 of the core system. It analyses the synthetic procedures and approaches to the formation of heterocycles from the fluoroquinolone carboxyl group and reveals the most convenient ways for such procedures. Further, the results of biological activity investigations for the obtained hybrid pharmacophore systems are presented. The latter revealed numerous promising molecules that can be further studied to overcome the problem of resistance to antibiotics, to find novel anticancer agents and more.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Comprehensive Review on Chemical Synthesis and Chemotherapeutic Potential of 3-Heteroaryl Fluoroquinolone Hybrids

et al. 2023

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“…[3] Recently, hybridization strategy has emerged as a novel approach involving the fusion of two or more pharmacophores in a single molecular skeleton, which can then have improved pharmacokinetic properties, higher target affinity, low tendency to induce resistance than the parent compound(s). [3][4][5][6][7][8][9] This has accelerated the development of new drugs, especially in the field of drug resistance.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Antibacterial Evaluation and Molecular Docking Studies of 1,3,4‐Oxadiazole‐2(3H)‐Thione‐Norfloxacin Hybrids as Potent Antibacterial Agents

et al. 2022

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Novel 1,3,4‐oxadiazole‐2(3H)‐thione‐norfloxacin hybrids were rationally designed based on the pharmacophore hybridization concept and yielded ten potent hybrids. All attained compounds were characterized applying electrospray ionization‐mass spectrometry, nuclear magnetic resonance, and Fourier‐transform infrared spectrophotometry. Compounds 3 c and 3 g were also characterized by single‐crystal X‐ray diffraction techniques. In vitro antibacterial activity of the attained hybrids was evaluated against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. All hybrids exhibited potent antibacterial activity against the test strains with MIC values between ≤0.125 and 1 μg/mL, which were more potent than the parent drug norfloxacin against P. aeruginosa. In particular, compounds 3 a, 3 e, and 3 f were more potent against S. aureus. The hybrid 3 e, with the smallest MIC and MBC against the test strains, showed rapid bactericidal activity in the time‐kill assays and eliminated S. aureus and E. coli <2 h of treatment. Meanwhile, cytotoxicity and hemolysis assays revealed low toxicity of the synthesized hybrids. Molecular docking studies indicated an improved receptor‐hybrid affinity towards DNA topoisomerase IV, showing a least binding energy of −9.4 to −10.0 kcal/mol. Among all the synthesized hybrids, 3 e can be a potential candidate for further antibiotic development.

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Design, Synthesis and Bio‐Evaluation of Novel Chalcones Bridged with 1,3,4‐Oxadiazole Linkers: ADMET and Docking Analysis

Gogisetti

Kanna

Sharma³

et al. 2022

Chemistry & Biodiversity

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In this article, we prepared a novel series of 1,3,4‐oxadiazoles containing chalcone analogs via replacement of phthalazine which had increased antibacterial activity and the final compounds were confirmed by proton, carbon nuclear magnetic resonance spectroscopy, infrared and mass spectral analysis. Two sets of 1,3,4‐oxadiazoles like 2‐methyl‐5‐substitutedbenzylthio‐1,3,4‐oxadiazolyl‐4‐methylphthalazine‐2‐ones (3a–f), (E)‐substituted phenyl acryloylphenyl‐4‐methyl‐1‐oxophthalazine‐1,3,4‐oxadiazolylthioacetamides (5a–f) were designed, synthesized and evaluated for their in vitro antibacterial potency against different Gram‐(+ve), Gram‐(–ve) microorganisms and fungal strains. The synthesized 4‐methyl‐2‐{[5‐({[2‐(trifluoromethyl)phenyl]methyl}sulfanyl)‐1,3,4‐oxadiazol‐2‐yl]methyl}phthalazin‐1(2H)‐one (3c), 4‐methyl‐2‐[(5‐{[(4‐nitrophenyl)methyl]sulfanyl}‐1,3,4‐oxadiazol‐2‐yl)methyl]phthalazin‐1(2H)‐one (3d), N‐(4‐{(2E)‐3‐[2‐(dimethylamino)phenyl]prop‐2‐enoyl}phenyl)‐2‐({5‐[(4‐methyl‐1‐oxophthalazin‐2(1H)‐yl)methyl]‐1,3,4‐oxadiazol‐2‐yl}sulfanyl)acetamide (5d), and N‐{4‐[(2E)‐3‐(3‐hydroxy‐4‐methoxyphenyl)prop‐2‐enoyl]phenyl}‐2‐({5‐[(4‐methyl‐1‐oxophthalazin‐2(1H)‐yl)methyl]‐1,3,4‐oxadiazol‐2‐yl}sulfanyl)acetamide (5e) displayed improved activity with MICs 1.41, 0.87, 2.16, 0.89 μg/mL as compared to the standard drugs rifamycin, ciprofloxacin, fluconazole (MIC=1.52, 1.94, 3.02 μg/mL). The prepared compounds were also analyzed with better target binding towards bacterial bioavailability, 5e exhibited highest bonds with amino acids ArgA45, LysA20, LysA17, ArgA171, AspA49, IleA14, HisA18 and having docking energy −8.68 Kcal/mol and dissociation constant 432.48 nM, respectively. These compounds were further evaluated for their ADMET and physicochemical properties by using SwissADME.

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Novel heterocyclic 1,3,4-oxadiazole derivatives of fluoroquinolones as a potent antibacterial agent: Synthesis and computational molecular modeling

Cited by 28 publications

References 39 publications

A Comprehensive Review on Chemical Synthesis and Chemotherapeutic Potential of 3-Heteroaryl Fluoroquinolone Hybrids

A Comprehensive Review on Chemical Synthesis and Chemotherapeutic Potential of 3-Heteroaryl Fluoroquinolone Hybrids

Synthesis, Antibacterial Evaluation and Molecular Docking Studies of 1,3,4‐Oxadiazole‐2(3H)‐Thione‐Norfloxacin Hybrids as Potent Antibacterial Agents

Design, Synthesis and Bio‐Evaluation of Novel Chalcones Bridged with 1,3,4‐Oxadiazole Linkers: ADMET and Docking Analysis

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