Synthesis of Novel Bis-pyrazole Derivatives as Antimicrobial Agents

Abstract

Background: bis-heterocycles especially those containing pyrazole moiety display much better antibacterial activity than mono heterocycles. Objective: Herein, we synthesised a series of new bis-pyrazoles and investigated their antimicrobial agents. Methods: A novel series of bis-pyrazole derivatives have been synthesized in good yield by coupling reaction of cyanoacetic acid 4-[(2-cyano-acetyl)-hydrazonomethyl]-benzylidene-hydrazide with a number of diazonium salts of aromatic amines in DMF in the presence of NaOH. Refluxing of the produced hydrazones with hydrazine-hydrate in ethanolic solution afforded the respective bis-pyrazoles. On the other hand, the reaction of bis(cyanoacetic acid hydrazide) derivative with a diversity of hydrazonoyl chlorides in dioxane under reflux gave bis-pyrazoles. Results: The structures of all the products were discussed and assured from all possible spectral data as well as for the elemental analysis. In addition, the results of the antimicrobial activity examination of selected derivatives revealed a high strength of some tested compounds compared to standard bactericides and fungicides utilized. Molecular docking of the newly synthesized compounds into the Enoyl ACP reductase active site supported the in vitro antimicrobial activity. All the tested compounds could fit in the enzyme binding pocket with significant binding affinities (-7.040 to -9.141 Kcal/mol). Conclusion: The good results of the antimicrobial examination of the newly synthesized bis-pyrazoles comprise the considerable evidence of the importance of bis-heterocyclic compounds which encourages us to continue designing and synthesising a novel series with potent biological activity in the future.

Design and Synthesis of Novel Pyrazoles, Pyrazolines, and Pyridines From Chalcone Derivatives With the Assessment of Their in Vitro Anticancer Activity Against T-47d and Uacc-257 Cell Lines

“…Pale yellow solid from glacial acetic acid, yield ( 1.16 g, 74%), mp: 151-152 0 C; IR (KBr, cm −1 ): 3032 (=C-H), 2931 (-C-H), 1662 (-C=O); 1 H-NMR: δ 2.22 (s, 3H, -COCH3), 2.85 (s, 6H, N-(CH3)2), 3.12 (dd, J = 4.1 and 13.6 Hz,1H, pyrazolinyl-H) , 3.80 (q, J = 11.6 and 6.1 Hz,1H, pyrazolinyl-H), 5.44 (dd, J = 4.0 and 7.5 Hz,1H, pyrazolinyl-H), 7.65 (d, J = 0.5 Hz, 1H, p-CH3-C6H3-H), 6.67 (d, J = 0.6 Hz,1H, p-CH3-C6H3-H), 6.98 (d, J = 0.6 Hz,1H, p-CH3-C6H3-H), 7.00 (d, J = 0.6 Hz,1H, p-CH3-C6H3-H), 7.15 (q, J = 3.7 and 1.2 Hz,1H, thienyl-H), 7.44 (dd, J = 0.1 and 3.0 Hz, 1H, thienyl-H), 7.72 (dd, J = 0.8 and 4.2 Hz, 1H, thienyl-H); MS (m/z, %): 315 (M+2, 3), 314 (M+1, 10), 313 (M+, 40), 312 (10), 204 (100), 203 (45), 196 (14), 189 (77), 162 (19), 147 (36), 146 (38) (14), 205 (19), 204 (74), 203 (39), 190 (18), 189 (100), 162 (28), 147 (60), 146 (70), 121 (18), 120 (17), 115 (23), 91 (37), 77 (31), 65 (20)…”

“…Pale yellow solid from glacial acetic acid, yield ( 1.58 g, 74%), mp: 250-251 0 C; IR (KBr, cm −1 ): 3380 (-N-H), 3149 (=C-H), 2221 (-CN), 1696 (-C=O); 1 H-NMR: δ 7.26 (s, 1H, thienyl-H), 7.43-7.90 (m, 11H, Ar-H + thienyl-H), 8.19 (s, 1H, Pyrazole-H), 9.12 (s, 1H, Pyridine-H); MS (m/z, %): 424 (M-2, 0.7), 321 (19), 320 (81), 277 (23), 276 (92), 129 (10), 104 (11), 95 (18), 85 (18), 84 (17), 83 (26), 81 (17), 77 (100), 69 (35), 57 (54), 55 (48), 51 (37)…”

“…Additionally pyrazoles, which are fivemembered two-nitrogen-containing heterocycles, are very important organic compounds. Numerous compounds containing pyrazole moiety are known to exhibit antidiabetic [16], analgesic [17], antiinflammatory [17,18], antipyretic [18], antimicrobial [19], antihypertensive [20] and anticancer [21,22] activities.…”

Carbonic Anhydrase Inhibition with Sulfonamides Incorporating Pyrazole- and Pyridazinecarboxamide Moieties Provides Examples of Isoform-Selective Inhibitors

“…In this context, the pyrazole scaffold is a versatile molecule that has attracted attention due to its wide range of diverse pharmacological activities, which make it a versatile lead molecule in several drug molecules such as celecoxib, ramifenazone, lonazolac, and rimonabant, drugs approved as COX-2 inhibitors [13][14][15][16], crizotinib [17] and paropanib [17] as anticancer drugs, sildenafil [17] (Viagra) PDE5 inhibitor, zometapine [18] as antidepressant, ocinaplon [19] as anxiolytic (Figure 1), and many others. Additionally, in recent years, their derivatives have been reported to possess antimicrobial activity [20][21][22] as well as antiviral [23,24], antidiabetic [25,26], anti-Alzheimer [27,28], antitubercular [29,30], and antileishmanial properties [31]. In this context, the pyrazole scaffold is a versatile molecule that has attracted attention due to its wide range of diverse pharmacological activities, which make it a versatile lead molecule in several drug molecules such as celecoxib, ramifenazone, lonazolac, and rimonabant, drugs approved as COX-2 inhibitors [13][14][15][16], crizotinib [17] and paropanib [17] as anticancer drugs, sildenafil [17] (Viagra) PDE5 inhibitor, zometapine [18] as antidepressant, ocinaplon [19] as anxiolytic (Figure 1), and many others.…”

Synthesis of Chitosan-La2O3 Nanocomposite and Its Utility as a Powerful Catalyst in the Synthesis of Pyridines and Pyrazoles

“…Extending our earlier efforts in the area of nanocatalysis [ 5 , 6 , 7 ], in this article La 2 O 3 nanoparticles immobilized onto the chitosan matrix were prepared ( Figure 1 ) and then employed as a promising heterogeneous basic catalyst to synthesis pyridines and pyrazoles. These azines and azoles have privileged antitumor [ 12 , 13 , 14 , 15 ], antidiabetes [ 16 ], antimicrobial [ 17 , 18 ], anti-HCV [ 14 , 19 , 20 ], and antidepressant [ 21 , 22 ] activities.…”