Synthesis of bulky-tailed sulfonamides incorporating pyrido[2,3- d ][1,2,4]triazolo[4,3- a ]pyrimidin-1(5H)-yl) moieties and evaluation of their carbonic anhydrases I, II, IV and IX inhibitory effects

Farès, Mohamed; Eladwy, Radwa A.; Nocentini, Alessio; Hadi, Soha R. Abd El; Ghabbour, Hazem A.; Abdel-Megeed, Ashraf M.; Eldehna, Wagdy M.; Abdel‐Aziz, Hatem A.; Supuran, Claudiu T.

doi:10.1016/j.bmc.2017.02.037

Cited by 40 publications

(9 citation statements)

References 54 publications

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“…The inhibition constants were obtained by non-linear least-squares methods using PRISM 3 and the Cheng-Prusoff equation as reported earlier, and represent the mean from at least three different determinations. The four tested CA isofoms were recombinant ones obtained in-house as reported earlier [26,27,28,29].…”

Section: Methodsmentioning

confidence: 99%

Novel Diamide-Based Benzenesulfonamides as Selective Carbonic Anhydrase IX Inhibitors Endowed with Antitumor Activity: Synthesis, Biological Evaluation and In Silico Insights

Abdelrahman

Eldehna

Nocentini

et al. 2019

IJMS

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In this work, we present the synthesis and biological evaluation of novel series of diamide-based benzenesulfonamides 5a–h as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, II, IX and XII. The target tumor-associated isoforms hCA IX and XII were undeniably the most affected ones (KIs: 8.3–123.3 and 9.8–134.5 nM, respectively). Notably, diamides 5a and 5h stood out as a single-digit nanomolar hCA IX inhibitors (KIs = 8.8 and 8.3 nM). The SAR outcomes highlighted that bioisosteric replacement of the benzylidene moiety, compounds 5a–g, with the hetero 2-furylidene moiety, compound 5h, achieved the best IX/I and IX/II selectivity herein reported with SIs of 985 and 13.8, respectively. Molecular docking simulations of the prepared diamides within CA IX active site revealed the ability of 5h to establish an additional H-bond between the heterocyclic oxygen and HE/Gln67. Moreover, benzenesulfonamides 5a, 5b and 5h were evaluated for their antitumor activity against renal cancer UO-31 cell line. Compound 5h was the most potent derivative with about 1.5-fold more enhanced activity (IC50 = 4.89 ± 0.22 μM) than the reference drug Staurosporine (IC50 = 7.25 ± 0.43 μM). Moreover, 5a and 5h were able to induce apoptosis in UO-31 cells as evidenced by the significant increase in the percent of annexinV-FITC positive apoptotic cells by 22.5- and 26.5-folds, respectively.

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Section: Methodsmentioning

confidence: 99%

Novel Diamide-Based Benzenesulfonamides as Selective Carbonic Anhydrase IX Inhibitors Endowed with Antitumor Activity: Synthesis, Biological Evaluation and In Silico Insights

Abdelrahman

Eldehna

Nocentini

et al. 2019

IJMS

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“…All chemical reagents and solvents were purchased from Aldrich (Munich, Germany). Compounds 2 [ 54 ]; 3a,b [ 55 ] and 5a,b [ 11 ] were synthesized according to their previous method.…”

Section: Methodsmentioning

confidence: 99%

Synthesis of arylidene hydrazinylpyrido[2,3-d]pyrimidin-4-ones as potent anti-microbial agents

Abdelhameed

Darwesh

El‐Shahat

2020

Heliyon

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Combination of arylidene hydrazinyl moiety with pyrido[2,3- d ]pyrimidin-4-one skeleton in compounds 7‒26 results in the output of unprecedented anti-microbial agents. Arylidene hydrazinyl based on Pyrido[2,3- d ]pyrimidin-4-one analoges 7‒26 prepared by the treatment of [2,3- d ]pyrimidin-4-ones 6a , b with various aromatic aldehydes. The antimicrobial action for recently synthesized compounds was considered towards gram positive bacterial species ( Staphylococcus aurous ATCC- 47077; Bacillus cereus ATCC-12228), gram negative bacterial species ( Escherichia coli ATCC-25922; Salmonella typhi ATCC-15566) and Candida albicans ATCC-10231 as fungal strains. The antimicrobial action expanded by expanding the electron donating group in position 2 and 5 for Pyrido[2,3- d ]pyrimidin-4-one core. Derivatives 13 , 14 , 15 , 16 and 12 ; individually appeared hopeful anti-microbial action towards all strains utilized with inhibition zone higher than that of standard reference drug with lowest MIC.

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“…All compounds were evaluated in vitro as inhibitors against a panel of different carbonic anhydrases (CA). The discovery of selective CA IX inhibitors resulted had an effective antitumour therapy (Fares et al, 2017 (Edupuganti et al, 2014). Bellacasa et al stated a series of 4-Amino-2-arylamino-6-(2,6-dichlorophenyl) substituted pyrido [2,3-d] pyrimidin-7-(8H)-ones and evaluated for treatment of non-Hodgkin's lymphomas.…”

Section: Methodologies For Pyridopyrimidine Scaffoldmentioning

confidence: 99%

An overview on synthetic and pharmaceutical prospective of pyrido[2,3‐d]pyrimidines scaffold

Yadav

Shah

2020

Chem Biol Drug Des

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Pyrido[2,3-d]pyrimidine, a fused hetero-bicyclic nucleus containing pyridine and pyrimidine rings has attained the momentary attention in the sphere of multicomponent synthetic protocol and medicinal chemist. Pyrido[2,3-d]pyrimidine derived drugs have manifested diverse pharmacological activities, particularly, anti-inflammatory, cytotoxic, antimicrobial, phosphodiesterase inhibitors and cytokine inhibitors etc. The present review illustrates various modern synthetic strategies adopted, the structure-activity relationship (SAR) aspects and discloses the extensive crucial biological properties (anticancer, anti-infectious, anti-diabetics and CNS agents) of pyrido[2,3-d]pyrimidines. K E Y W O R D S anticancer, anti-diabetics, anti-infectious, CNS agents, pyrido[2,3-d]pyrimidines How to cite this article: Yadav P, Shah K. An overview on synthetic and pharmaceutical prospective of pyrido[2,3-d]pyrimidines scaffold.

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Synthesis of bulky-tailed sulfonamides incorporating pyrido[2,3- d ][1,2,4]triazolo[4,3- a ]pyrimidin-1(5H)-yl) moieties and evaluation of their carbonic anhydrases I, II, IV and IX inhibitory effects

Cited by 40 publications

References 54 publications

Novel Diamide-Based Benzenesulfonamides as Selective Carbonic Anhydrase IX Inhibitors Endowed with Antitumor Activity: Synthesis, Biological Evaluation and In Silico Insights

Novel Diamide-Based Benzenesulfonamides as Selective Carbonic Anhydrase IX Inhibitors Endowed with Antitumor Activity: Synthesis, Biological Evaluation and In Silico Insights

Synthesis of arylidene hydrazinylpyrido[2,3-d]pyrimidin-4-ones as potent anti-microbial agents

An overview on synthetic and pharmaceutical prospective of pyrido[2,3‐d]pyrimidines scaffold

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