Discovery of new chromone containing sulfonamides as potent inhibitors of bovine cytosolic carbonic anhydrase

al‐Rashida, Mariya; Ashraf, Muhammad; Hussain, Bushra; Nagra, Saeed Ahmad; Abbas, Ghulam

doi:10.1016/j.bmc.2011.04.040

Cited by 28 publications

(20 citation statements)

References 30 publications

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“…31,32 Acetazolamide was used as a standard inhibitor with an IC 50 value of 0.96 ± 0.18 µM. 31,32 Acetazolamide was used as a standard inhibitor with an IC 50 value of 0.96 ± 0.18 µM.…”

Section: Carbonic Anhydrase Inhibitionmentioning

confidence: 99%

Exploiting the potential of aryl acetamide derived Zn(ii) complexes in medicinal chemistry: synthesis, structural analysis, assessment of biological profile and molecular docking studies

et al. 2016

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In the medical arena, advancements in the rational design of metal-based therapeutic agents showcase increasingly significant research attempts towards the development of new compounds with fewer toxic side effects. In this context, our present manuscript explicitly encapsulates the design and synthesis of Zn(II) complexes derived from different aryl acetamides, as potential frontline enzyme inhibitors as well as antileishmanial and anticancer agents. The structures of synthesized metal complexes were established on the basis of spectro-analytical data and, in case of 4c, by single crystal X-ray diffraction analysis. The X-ray structure of Zn(II) complex, dichlorido-bis[N-(4-methoxyphenyl)acetamide-O]-zinc(II), 4c, showed the zinc atom and the chlorido ligands to lie on a mirror plane with the acetamide ligands in general positions. The coordination geometry of the zinc atom was tetrahedral with the N-(4-methoxyphenyl)acetamide ligands bound to zinc via the acetamide oxygens. The designed coordination complexes were analysed for their enzyme inhibition potential, anticancer and antileishmanial efficacy. Detailed kinetics studies for complex 4b, the most active carbonic anhydrase and alkaline phosphatase inhibitor, indicated a competitive and uncompetitive mode of inhibition against carbonic anhydrase and tissue non-specific alkaline phosphatase, respectively. The bioactivity results and molecular docking analysis revealed that the synthesized coordination complexes (4a-c) hold great potential to be developed as promising enzyme inhibitors in addition to the anticancer and anti-parasitic drug candidates. disorders. 1 In this quest, several coordination compounds have been synthesized involving different metal center like copper, zinc, cobalt, nickel, gold and antimony. 2,3 In addition, a variety of mononuclear metal complexes with different ligands have been shown to be effective for cancer therapy both in vitro and in vivo. 4-8 Transition metal complexes with platinum, gold, palladium and ruthenium metal centers are under various stages of clinical trials. 9,10 Interest in zinc complexes stems from their wide and increasing utility in medicinal chemistry. In addition, zinc is considered as the most abundant trace intracellular element with its substantial occurrence in the nucleus. 11 Furthermore, Zn(II) ions are present in zinc finger proteins that recognize and bind to DNA. 12,13 Several Zn(II) and other metal complexes with a variety of ligands have been reported in the literature with different coordination modes displaying a unique spectrum of biological functions including antitumor, antioxidant, xanthine oxidase, anticonvulsant, antimicrobial and antileishmanicidal activities. 14 Also, various metal complexes with different coordination ligands have emerged as inhibitors of carbonic anhydrases, 15 cholinesterase, 16 and alkaline phosphatases. 17 However, there is still an unmet need for the development of coordination complexes with unique and multifaceted biological profile.Hence, a combination of all com...

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“…31,32 Acetazolamide was used as a standard inhibitor with an IC 50 value of 0.96 ± 0.18 µM. 31,32 Acetazolamide was used as a standard inhibitor with an IC 50 value of 0.96 ± 0.18 µM.…”

Section: Carbonic Anhydrase Inhibitionmentioning

confidence: 99%

Exploiting the potential of aryl acetamide derived Zn(ii) complexes in medicinal chemistry: synthesis, structural analysis, assessment of biological profile and molecular docking studies

et al. 2016

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“…The inhibition profile of various CA isozymes with this class of agents is very variable, with inhibition constants ranging from the millimolar to the submicromolar range 10 . Thus, it seemed reasonable to us to extend the previous studies 8,10,[18][19][20][21][22][23][24][25][26][27][28][29] , including in this investigation a series of Schiff's bases obtained by condensing formylchromone with aminosulfonamides 11 . The purification of the three CA isozymes was performed with a simple one step method by a Sepharose-4B-aniline-sulfanilamide affinity column chromatoghrapy 9,18 .…”

Section: Journal Of Enzyme Inhibition and Medicinal Chemistrymentioning

confidence: 89%

“…The sulfonamide CAI acetazolamide AZA [1][2][3][4] has been used as a negative control in our experiments, and for comparison reasons. The previous reports by al-Rashida et al 11 investigated compounds 1-5 with bovine carbonic anhydrase (bCA). Data of Table 1 show the following regarding inhibition of hCA I, II and VI with compounds 1-9 and AZA (as standard), by an hydratase assay, with CO 2 as substrate 15 : (i) Against the slow cytosolic isozyme hCA I, compounds 1-9 behave as quite weak inhibitors, with K i values in the range of 13.724-118.47 μM.…”

Section: Journal Of Enzyme Inhibition and Medicinal Chemistrymentioning

confidence: 99%

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Chromone containing sulfonamides as potent carbonic anhydrase inhibitors

Ekinci

al‐Rashida

Abbas

et al. 2011

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…On the other hand, reaction of 3-formylchromones 1a-c with equimolar ratio of aryl/hetarylamines 157 in boiling ethanol gave 3-(aryl/hetarylaminomethylene)-2-(ethoxy) chromones 158, but when the reaction took place with two moles of 157 in dry toluene, the 1,4-adducts 159 were obtained (Scheme 77) [105][106][107][108][109][110][111][112][113][114][115].…”

Section: Scheme 76mentioning

confidence: 99%