COX-1/COX-2 inhibition activities and molecular docking study of newly designed and synthesized pyrrolo[3,4-c]pyrrole Mannich bases

Redzicka, Aleksandra; Szczukowski, Łukasz; Kochel, Andrzej; Wiatrak, Benita; Gębczak, Katarzyna; Czyżnikowska, Żaneta

doi:10.1016/j.bmc.2019.07.033

Cited by 21 publications

(23 citation statements)

References 54 publications

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“…The presence of this bioactive group is identified with enhanced pharmacological activity of designed pyrrolo[3,4-d]pyridazinone derivatives. Arylpiperazine or arylpiperidine pharmacophore, which are present in the structure of investigated molecules 10b and 13b, can also be distinguished in many drugs and new drug candidates (Figure 8, IV) [4][5][6][7][8][9][10][35][36][37]39,40]. According to literature reports, the introduction of the electron-withdrawing substituent in position 4 of the aryl ring in that moiety often results in enhanced pharmacological activity of the final compounds.…”

Section: Discussionmentioning

confidence: 96%

Novel 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-d]pyridazinone Exert Antinociceptive Activity in the Tail-Flick and Formalin Test in Rodents and Reveal Reduced Gastrotoxicity

Szandruk-Bender

Wiatrak

Szczukowski

et al. 2020

IJMS

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Despite the availability of the current drug arsenal for pain management, there is still a clinical need to identify new, more effective, and safer analgesics. Based on our earlier study, newly synthesized 1,3,4-oxadiazole derivatives of pyrrolo[3,4-d]pyridazinone, especially 10b and 13b, seem to be promising as potential analgesics. The current study was designed to investigate whether novel derivatives attenuate nociceptive response in animals subjected to thermal or chemical noxious stimulus, and to compare this effect to reference drugs. The antinociceptive effect of novel compounds was studied using the tail-flick and formalin test. Pretreatment with novel compounds at all studied doses increased the latency time in the tail-flick test and decreased the licking time during the early phase of the formalin test. New derivatives given at the medium and high doses also reduced the late phase of the formalin test. The achieved results indicate that new derivatives dose-dependently attenuate nociceptive response in both models of pain and exert a lack of gastrotoxicity. Both studied compounds act more efficiently than indomethacin, but not morphine. Compound 13b at the high dose exerts the greatest antinociceptive effect. It may be due to the reduction of nociceptor sensitization via prostaglandin E2 and myeloperoxidase levels decrease.

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Section: Discussionmentioning

confidence: 96%

Novel 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-d]pyridazinone Exert Antinociceptive Activity in the Tail-Flick and Formalin Test in Rodents and Reveal Reduced Gastrotoxicity

Szandruk-Bender

Wiatrak

Szczukowski

et al. 2020

IJMS

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“…We have recently reported on the synthesis and COX-1/COX-2 inhibition of N-substituted cyclic imides (Figure 2) [39]. We have recently reported on the synthesis and COX-1/COX-2 inhibition of Nsubstituted cyclic imides (Figure 2) [39].…”

Section: Introductionmentioning

confidence: 97%

“…2021, 22, x FOR PEER REVIEW The obtained structures (Figure 2) inhibited less COX-2 an reference drug-meloxicam. Therefore, their selectivity ratio (C than twice as high as meloxicam [39].…”

Section: Introductionmentioning

confidence: 99%

“…The imide core is also present in compounds whose activity is related to CNS activity [32][33][34][35][36]. In particular, much attention has been paid to their ability to inhibit cyclooxygenases, anti-inflammatory, and analgetic activity [37][38][39][40][41][42][43][44][45][46][47]. To date, several drugs with cyclic imide structure have been approved, including lurasidone, buspirone, ethosuximide, mesuximide, and the IMiDs class includes thalidomide and its analogues lenalidomide, pomalidomide, apremilast (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

“…2021, 22, x FOR PEER REVIEW 2 of 21 neutral and hydrophobic, which determines their ability to penetrate biological membranes [9,50,53]. We have recently reported on the synthesis and COX-1/COX-2 inhibition of N-substituted cyclic imides (Figure 2) [39]. We have recently reported on the synthesis and COX-1/COX-2 inhibition of Nsubstituted cyclic imides (Figure 2) [39].…”

Section: Introductionmentioning

confidence: 99%

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Design and Synthesis of N-Substituted 3,4-Pyrroledicarboximides as Potential Anti-Inflammatory Agents

Redzicka

Czyżnikowska

Wiatrak

et al. 2021

IJMS

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In the present paper, we describe the biological activity of the newly designed and synthesized series N-substituted 3,4-pyrroledicarboximides 2a–2p. The compounds 2a–2p were obtained in good yields by one-pot, three-component condensation of pyrrolo[3,4-c]pyrrole scaffold (1a–c) with secondary amines and an excess of formaldehyde solution in C2H5OH. The structural properties of the compounds were characterized by 1H NMR, 13C NMR FT-IR, MS, and elemental analysis. Moreover, single crystal X-ray diffraction has been recorded for compound 2h. The colorimetric inhibitor screening assay was used to obtain their potencies to inhibit COX-1 and COX-2 enzymes. According to the results, all of the tested compounds inhibited the activity of COX-1 and COX-2. Theoretical modeling was also applied to describe the binding properties of compounds towards COX-1 and COX-2 cyclooxygenase isoform. The data were supported by QSAR study.

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Utility of pyrrole‐2‐thioacetohydrazide in synthesis of new heterocyclic compounds with promising antimicrobial activities and molecular docking studies

El-Sayed

El‐Remaily

Salama

et al. 2021

Journal of Heterocyclic Chem

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One‐pot synthetic method for [(3‐cyano‐5‐phenyl‐1H‐pyrrol‐2‐yl)sulfanyl]acetic acids 3a,b with excellent yield have been accomplished via a tetrabutylammonium bromide (TBAB) catalyzed reaction of mercaptoacetic acid with 2‐(2‐oxo‐2‐arylethyl) malononitrile under phase transfer catalysis conditions (PTC). The coupling of methyl [(3‐cyano‐5‐phenyl‐1H‐pyrrol‐2‐yl)sulfanyl] acetate 4a,b with hydrazine gave the corresponding 2‐[(3‐cyano‐5‐aryl‐1H‐pyrrol‐2yl)thio] acetohydrazides 5a,b, which reacted with glucose, acetylacetone, carbon disulfide, phenyl isothiocyanate, chloroacetyl chloride or benzaldehyde, to afford the compounds 6a,b–11a,b, respectively ranged from satisfactory to excellent yields. In vitro antibacterial and antifungal activities were assessed with good results. Furthermore, molecular docking experiments were done for the most active compounds against the E. coli MurB enzyme in order to determine the mechanism of their antibacterial activity and showed good binding interactions.

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COX-1/COX-2 inhibition activities and molecular docking study of newly designed and synthesized pyrrolo[3,4-c]pyrrole Mannich bases

Cited by 21 publications

References 54 publications

Novel 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-d]pyridazinone Exert Antinociceptive Activity in the Tail-Flick and Formalin Test in Rodents and Reveal Reduced Gastrotoxicity

Novel 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-d]pyridazinone Exert Antinociceptive Activity in the Tail-Flick and Formalin Test in Rodents and Reveal Reduced Gastrotoxicity

Design and Synthesis of N-Substituted 3,4-Pyrroledicarboximides as Potential Anti-Inflammatory Agents

Utility of pyrrole‐2‐thioacetohydrazide in synthesis of new heterocyclic compounds with promising antimicrobial activities and molecular docking studies

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