Synthesis and biological evaluation of novel 3-(quinolin-4-ylamino)benzenesulfonamidesAQ3 as carbonic anhydrase isoforms I and II inhibitors

doi:10.1080/14756366.2019.1652282

. 2019 Dec;34(1):1457-1464.

doi: 10.1080/14756366.2019.1652282.

Synthesis and biological evaluation of novel 3-(quinolin-4-ylamino)benzenesulfonamidesAQ3 as carbonic anhydrase isoforms I and II inhibitors

Mohammad M Al-Sanea¹, Ahmed Elkamhawy^{2

3}, Sora Paik², Silvia Bua⁴, So Ha Lee², Mohamed A Abdelgawad^{1

5}, Eun Joo Roh^{2

6}, Wagdy M Eldehna⁷, Claudiu T Supuran⁴

Affiliations

¹ a Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University , Sakaka , Saudi Arabia.
² b Chemical Kinomics Research Center, Korea Institute of Science and Technology (KIST) , Seoul , Republic of Korea.
³ c Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University , Mansoura , Egypt.
⁴ d Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence , Firenze , Italy.
⁵ e Department of Pharmaceutical Organic Chemistry, Beni-Suef University , Beni-Suef , Egypt.
⁶ f Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology , Seoul , Republic of Korea.
⁷ g Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University , Kafrelsheikh , Egypt.

PMID: 31411080
PMCID: PMC6713088
DOI: 10.1080/14756366.2019.1652282

Synthesis and biological evaluation of novel 3-(quinolin-4-ylamino)benzenesulfonamidesAQ3 as carbonic anhydrase isoforms I and II inhibitors

Mohammad M Al-Sanea et al. J Enzyme Inhib Med Chem. 2019 Dec.

. 2019 Dec;34(1):1457-1464.

doi: 10.1080/14756366.2019.1652282.

Authors

Mohammad M Al-Sanea¹, Ahmed Elkamhawy^{2

3}, Sora Paik², Silvia Bua⁴, So Ha Lee², Mohamed A Abdelgawad^{1

5}, Eun Joo Roh^{2

6}, Wagdy M Eldehna⁷, Claudiu T Supuran⁴

Affiliations

¹ a Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University , Sakaka , Saudi Arabia.
² b Chemical Kinomics Research Center, Korea Institute of Science and Technology (KIST) , Seoul , Republic of Korea.
³ c Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University , Mansoura , Egypt.
⁴ d Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence , Firenze , Italy.
⁵ e Department of Pharmaceutical Organic Chemistry, Beni-Suef University , Beni-Suef , Egypt.
⁶ f Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology , Seoul , Republic of Korea.
⁷ g Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University , Kafrelsheikh , Egypt.

PMID: 31411080
PMCID: PMC6713088
DOI: 10.1080/14756366.2019.1652282

Abstract

Carbonic anhydrases (CAs, EC 4.2.1.1) are crucial metalloenzymes that are involved in diverse bioprocesses. We report the synthesis and biological evaluation of novel series of benzenesulfonamides incorporating un/substituted ethyl quinoline-3-carboxylate moieties. The newly synthesised compounds were in vitro evaluated as inhibitors of the cytosolic human (h) isoforms hCA I and II. Both isoforms hCA I and II were inhibited by the quinolines reported here in variable degrees: hCA I was inhibited with K_Is in the range of 0.966-9.091 μM, whereas hCA II in the range of 0.083-3.594 μM. The primary 7-chloro-6-flouro substituted sulphfonamide derivative 6e (K_I = 0.083 μM) proved to be the most active quinoline in inhibiting hCA II, whereas, its secondary sulfonamide analog failed to inhibit the hCA II up to 10 μM, confirming the crucial role of the primary sulphfonamide group, as a zinc-binding group for CA inhibitory activity.

Keywords: carbonic anhydrase; cytosolic isoforms hCA I and II; quinolines; synthesis.

PubMed Disclaimer

Figures

**Figure 1.**
Structures of some approved CAIs antiglaucoma drugs, and the target quinolines **6a–f** and 11.

**Scheme 1.**
Synthesis of target quinolines **6a–f**; *Reagents and conditions*: (i) DEEMM/Ethanol/reflux 1 h; (ii) Diphenyl ether/250 °C/45 min; (**iii**) POCl₃/reflux 1 h; (iv) Absolute ethyl alcohol/reflux 4 h.

**Scheme 2.**
Synthesis of target quinoline 11; *Reagents and conditions*: (i) Hunig's Base/THF/stirring at r.t./1 h; (ii) H₂/10% Pd/C/MeOH/r.t.; (**iii**) Compound 4e/Absolute ethyl alcohol/reflux 4 h.

See this image and copyright information in PMC

Cited by

Novel benzofuran-based sulphonamides as selective carbonic anhydrases IX and XII inhibitors: synthesis and in vitro biological evaluation.
Abdelrahman MA, Eldehna WM, Nocentini A, Ibrahim HS, Almahli H, Abdel-Aziz HA, Abou-Seri SM, Supuran CT. Abdelrahman MA, et al. J Enzyme Inhib Med Chem. 2020 Dec;35(1):298-305. doi: 10.1080/14756366.2019.1697250. J Enzyme Inhib Med Chem. 2020. PMID: 31809607 Free PMC article.
Development of Novel Quinoline-Based Sulfonamides as Selective Cancer-Associated Carbonic Anhydrase Isoform IX Inhibitors.
Shaldam M, Nocentini A, Elsayed ZM, Ibrahim TM, Salem R, El-Domany RA, Capasso C, Supuran CT, Eldehna WM. Shaldam M, et al. Int J Mol Sci. 2021 Oct 15;22(20):11119. doi: 10.3390/ijms222011119. Int J Mol Sci. 2021. PMID: 34681794 Free PMC article.
Design, synthesis and molecular docking of new fused 1H-pyrroles, pyrrolo[3,2-d]pyrimidines and pyrrolo[3,2-e][1, 4]diazepine derivatives as potent EGFR/CDK2 inhibitors.
Belal A, Abdel Gawad NM, Mehany ABM, Abourehab MAS, Elkady H, Al-Karmalawy AA, Ismael AS. Belal A, et al. J Enzyme Inhib Med Chem. 2022 Dec;37(1):1884-1902. doi: 10.1080/14756366.2022.2096019. J Enzyme Inhib Med Chem. 2022. PMID: 35801486 Free PMC article.
Uracil as a Zn-Binding Bioisostere of the Allergic Benzenesulfonamide in the Design of Quinoline-Uracil Hybrids as Anticancer Carbonic Anhydrase Inhibitors.
El-Kalyoubi SA, Taher ES, Ibrahim TS, El-Behairy MF, Al-Mahmoudy AMM. El-Kalyoubi SA, et al. Pharmaceuticals (Basel). 2022 Apr 19;15(5):494. doi: 10.3390/ph15050494. Pharmaceuticals (Basel). 2022. PMID: 35631321 Free PMC article.
Topo II inhibition and DNA intercalation by new phthalazine-based derivatives as potent anticancer agents: design, synthesis, anti-proliferative, docking, and in vivo studies.
Khalifa MM, Al-Karmalawy AA, Elkaeed EB, Nafie MS, Tantawy MA, Eissa IH, Mahdy HA. Khalifa MM, et al. J Enzyme Inhib Med Chem. 2022 Dec;37(1):299-314. doi: 10.1080/14756366.2021.2007905. J Enzyme Inhib Med Chem. 2022. PMID: 34894955 Free PMC article.

See all "Cited by" articles

References

1. (a) Supuran CT. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat Rev Drug Discov 2008;7:168–81., - PubMed
2. (b) Alterio V, Di Fiore A, D’Ambrosio K, et al. . Multiple binding modes of inhibitors to carbonic anhydrases: how to design specific drugs targeting 15 different isoforms? Chem Rev 2012;112:4421–68., - PubMed
3. (c) Supuran CT. Applications of carbonic anhydrases inhibitors in renal and central nervous system diseases. Expert Opin Ther Pat 2018;28:713–21., - PubMed
4. (d) Supuran CT. Carbonic anhydrase inhibitors and their potential in a range of therapeutic areas. Expert Opin Ther Pat 2018;28:709–12., - PubMed
5. (e) Supuran CT. Carbonic anhydrase inhibitors as emerging agents for the treatment and imaging of hypoxic tumors. Expert Opin Investig Drugs 2018;27:963–70., - PubMed
6. (f) Nocentini A, Supuran CT. Carbonic anhydrase inhibitors as antitumor/antimetastatic agents: a patent review (2008-2018). Expert Opin Ther Pat 2018;28:729–40. - PubMed
1. (a) Supuran CT. Structure-based drug discovery of carbonic anhydrase inhibitors. J Enzyme Inhib Med Chem 2012;27:759–72., - PubMed
2. (b) De Simone G, Supuran CT. (In)organic anions as carbonic anhydrase inhibitors. J Inorg Biochem 2012;111:117–29., - PubMed
3. (c) Supuran CT. Carbonic anhydrase inhibition and the management of hypoxic tumors. Metabolites 2017;7:E48, - PMC - PubMed
4. (d) Supuran CT. Carbonic anhydrases and metabolism. Metabolites 2018;8:E25., - PMC - PubMed
5. (e) Supuran CT. Carbon- versus sulphur-based zinc binding groups for carbonic anhydrase inhibitors? J Enzyme Inhib Med Chem 2018;33:485–95. - PMC - PubMed
1. (a) Supuran CT. Carbonic anhydrase inhibitors. Bioorg Med Chem Lett 2010;20:3467–74., - PubMed
2. (b) Briganti F, Pierattelli R, Scozzafava A, Supuran CT. Carbonic anhydrase inhibitors. Part 37. Novel classes of carbonic anhydrase inhibitors and their interaction with the native and cobalt-substituted enzyme: kinetic and spectroscopic investigations. Eur J Med Chem 1996;31:1001–10.,
3. (c) Supuran CT. How many carbonic anhydrase inhibition mechanisms exist? J Enzyme Inhib Med Chem 2016;31:345–60., - PubMed
4. (d) Supuran CT. Advances in structure-based drug discovery of carbonic anhydrase inhibitors. Expert Opin Drug Discov 2017;12:61–88., - PubMed
5. (e) Supuran CT. Structure and function of carbonic anhydrases. Biochem J 2016;473:2023–32., - PubMed
6. (f) Neri D, Supuran CT. Interfering with pH regulation in tumours as a therapeutic strategy. Nat Rev Drug Discov 2011;10:767–77., - PubMed
7. (g) Supuran CT, Vullo D, Manole G, et al. . Designing of novel carbonic anhydrase inhibitors and activators. Curr Med Chem Cardiovasc Hematol Agents 2004;2:49–68. - PubMed
1. (a) Pastorekova S, Parkkila S, Pastorek J, Supuran CT. Carbonic anhydrases: current state of the art, therapeutic applications and future prospects. J Enzyme Inhib Med Chem 2004;19:199–229., - PubMed
2. (b) Supuran CT, Capasso C. The eta-class carbonic anhydrases as drug targets for antimalarial agents. Expert Opin Ther Targets 2015;19:551–63., - PubMed
3. (c) Capasso C, Supuran CT. Bacterial, fungal and protozoan carbonic anhydrases as drug targets. Expert Opin Ther Targets 2015;19:1689–704., - PubMed
4. (d) Supuran CT, Capasso C. Biomedical applications of prokaryotic carbonic anhydrases. Expert Opin Ther Pat 2018;28:745–54., - PubMed
5. (e) Supuran CT, Capasso C. An overview of the bacterial carbonic anhydrases. Metabolites 2017;7:56. - PMC - PubMed
1. (a) Supuran CT. Carbonic anhydrase inhibitors and activators for novel therapeutic applications. Future Med Chem 2011;3:1165–80., - PubMed
2. (b) Akocak S, Lolak N, Bua S, et al. . Discovery of novel 1,3-diaryltriazene sulfonamides as carbonic anhydrase I, II, VII, and IX inhibitors. J Enzyme Inhib Med Chem 2018;33:1575–80., - PMC - PubMed
3. (c) Winum JY, Temperini C, El Cheikh K, et al. . Carbonic anhydrase inhibitors: clash with Ala65 as a means for designing inhibitors with low affinity for the ubiquitous isozyme II, exemplified by the crystal structure of the topiramate sulfamide analogue. J Med Chem 2006;49:7024–31., - PubMed
4. (d) Supuran CT. Carbonic anhydrase inhibitors in the treatment and prophylaxis of obesity. Expert Opin Ther Pat 2003;13:1545–50.

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions

Grants and funding

This research was supported by Jouf University (Grant 39/480), the KIST Institutional programs (Grant No. 2E29260) from Korea Institute of Science and Technology, and by the Creative Fusion Research Program through the Creative Allied Project funded by the National Research Council of Science & Technology (CAP-12–1-KIST).

LinkOut - more resources

Full Text Sources

[1] (a) Supuran CT. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat Rev Drug Discov 2008;7:168–81., - PubMed

(b) Alterio V, Di Fiore A, D’Ambrosio K, et al. . Multiple binding modes of inhibitors to carbonic anhydrases: how to design specific drugs targeting 15 different isoforms? Chem Rev 2012;112:4421–68., - PubMed

(c) Supuran CT. Applications of carbonic anhydrases inhibitors in renal and central nervous system diseases. Expert Opin Ther Pat 2018;28:713–21., - PubMed

(d) Supuran CT. Carbonic anhydrase inhibitors and their potential in a range of therapeutic areas. Expert Opin Ther Pat 2018;28:709–12., - PubMed

(e) Supuran CT. Carbonic anhydrase inhibitors as emerging agents for the treatment and imaging of hypoxic tumors. Expert Opin Investig Drugs 2018;27:963–70., - PubMed

(f) Nocentini A, Supuran CT. Carbonic anhydrase inhibitors as antitumor/antimetastatic agents: a patent review (2008-2018). Expert Opin Ther Pat 2018;28:729–40. - PubMed

[2] (a) Supuran CT. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat Rev Drug Discov 2008;7:168–81., - PubMed

[3] (b) Alterio V, Di Fiore A, D’Ambrosio K, et al. . Multiple binding modes of inhibitors to carbonic anhydrases: how to design specific drugs targeting 15 different isoforms? Chem Rev 2012;112:4421–68., - PubMed

[4] (c) Supuran CT. Applications of carbonic anhydrases inhibitors in renal and central nervous system diseases. Expert Opin Ther Pat 2018;28:713–21., - PubMed

[5] (d) Supuran CT. Carbonic anhydrase inhibitors and their potential in a range of therapeutic areas. Expert Opin Ther Pat 2018;28:709–12., - PubMed

[6] (e) Supuran CT. Carbonic anhydrase inhibitors as emerging agents for the treatment and imaging of hypoxic tumors. Expert Opin Investig Drugs 2018;27:963–70., - PubMed

[7] (f) Nocentini A, Supuran CT. Carbonic anhydrase inhibitors as antitumor/antimetastatic agents: a patent review (2008-2018). Expert Opin Ther Pat 2018;28:729–40. - PubMed

[8] (a) Supuran CT. Structure-based drug discovery of carbonic anhydrase inhibitors. J Enzyme Inhib Med Chem 2012;27:759–72., - PubMed

(b) De Simone G, Supuran CT. (In)organic anions as carbonic anhydrase inhibitors. J Inorg Biochem 2012;111:117–29., - PubMed

(c) Supuran CT. Carbonic anhydrase inhibition and the management of hypoxic tumors. Metabolites 2017;7:E48, - PMC - PubMed

(d) Supuran CT. Carbonic anhydrases and metabolism. Metabolites 2018;8:E25., - PMC - PubMed

(e) Supuran CT. Carbon- versus sulphur-based zinc binding groups for carbonic anhydrase inhibitors? J Enzyme Inhib Med Chem 2018;33:485–95. - PMC - PubMed

[9] (a) Supuran CT. Structure-based drug discovery of carbonic anhydrase inhibitors. J Enzyme Inhib Med Chem 2012;27:759–72., - PubMed

[10] (b) De Simone G, Supuran CT. (In)organic anions as carbonic anhydrase inhibitors. J Inorg Biochem 2012;111:117–29., - PubMed

[11] (c) Supuran CT. Carbonic anhydrase inhibition and the management of hypoxic tumors. Metabolites 2017;7:E48, - PMC - PubMed

[12] (d) Supuran CT. Carbonic anhydrases and metabolism. Metabolites 2018;8:E25., - PMC - PubMed

[13] (e) Supuran CT. Carbon- versus sulphur-based zinc binding groups for carbonic anhydrase inhibitors? J Enzyme Inhib Med Chem 2018;33:485–95. - PMC - PubMed

[14] (a) Supuran CT. Carbonic anhydrase inhibitors. Bioorg Med Chem Lett 2010;20:3467–74., - PubMed

(b) Briganti F, Pierattelli R, Scozzafava A, Supuran CT. Carbonic anhydrase inhibitors. Part 37. Novel classes of carbonic anhydrase inhibitors and their interaction with the native and cobalt-substituted enzyme: kinetic and spectroscopic investigations. Eur J Med Chem 1996;31:1001–10.,

(c) Supuran CT. How many carbonic anhydrase inhibition mechanisms exist? J Enzyme Inhib Med Chem 2016;31:345–60., - PubMed

(d) Supuran CT. Advances in structure-based drug discovery of carbonic anhydrase inhibitors. Expert Opin Drug Discov 2017;12:61–88., - PubMed

(e) Supuran CT. Structure and function of carbonic anhydrases. Biochem J 2016;473:2023–32., - PubMed

(f) Neri D, Supuran CT. Interfering with pH regulation in tumours as a therapeutic strategy. Nat Rev Drug Discov 2011;10:767–77., - PubMed

(g) Supuran CT, Vullo D, Manole G, et al. . Designing of novel carbonic anhydrase inhibitors and activators. Curr Med Chem Cardiovasc Hematol Agents 2004;2:49–68. - PubMed

[15] (a) Supuran CT. Carbonic anhydrase inhibitors. Bioorg Med Chem Lett 2010;20:3467–74., - PubMed

[16] (b) Briganti F, Pierattelli R, Scozzafava A, Supuran CT. Carbonic anhydrase inhibitors. Part 37. Novel classes of carbonic anhydrase inhibitors and their interaction with the native and cobalt-substituted enzyme: kinetic and spectroscopic investigations. Eur J Med Chem 1996;31:1001–10.,

[17] (c) Supuran CT. How many carbonic anhydrase inhibition mechanisms exist? J Enzyme Inhib Med Chem 2016;31:345–60., - PubMed

[18] (d) Supuran CT. Advances in structure-based drug discovery of carbonic anhydrase inhibitors. Expert Opin Drug Discov 2017;12:61–88., - PubMed

[19] (e) Supuran CT. Structure and function of carbonic anhydrases. Biochem J 2016;473:2023–32., - PubMed

[20] (f) Neri D, Supuran CT. Interfering with pH regulation in tumours as a therapeutic strategy. Nat Rev Drug Discov 2011;10:767–77., - PubMed

[21] (g) Supuran CT, Vullo D, Manole G, et al. . Designing of novel carbonic anhydrase inhibitors and activators. Curr Med Chem Cardiovasc Hematol Agents 2004;2:49–68. - PubMed

[22] (a) Pastorekova S, Parkkila S, Pastorek J, Supuran CT. Carbonic anhydrases: current state of the art, therapeutic applications and future prospects. J Enzyme Inhib Med Chem 2004;19:199–229., - PubMed

(b) Supuran CT, Capasso C. The eta-class carbonic anhydrases as drug targets for antimalarial agents. Expert Opin Ther Targets 2015;19:551–63., - PubMed

(c) Capasso C, Supuran CT. Bacterial, fungal and protozoan carbonic anhydrases as drug targets. Expert Opin Ther Targets 2015;19:1689–704., - PubMed

(d) Supuran CT, Capasso C. Biomedical applications of prokaryotic carbonic anhydrases. Expert Opin Ther Pat 2018;28:745–54., - PubMed

(e) Supuran CT, Capasso C. An overview of the bacterial carbonic anhydrases. Metabolites 2017;7:56. - PMC - PubMed

[23] (a) Pastorekova S, Parkkila S, Pastorek J, Supuran CT. Carbonic anhydrases: current state of the art, therapeutic applications and future prospects. J Enzyme Inhib Med Chem 2004;19:199–229., - PubMed

[24] (b) Supuran CT, Capasso C. The eta-class carbonic anhydrases as drug targets for antimalarial agents. Expert Opin Ther Targets 2015;19:551–63., - PubMed

[25] (c) Capasso C, Supuran CT. Bacterial, fungal and protozoan carbonic anhydrases as drug targets. Expert Opin Ther Targets 2015;19:1689–704., - PubMed

[26] (d) Supuran CT, Capasso C. Biomedical applications of prokaryotic carbonic anhydrases. Expert Opin Ther Pat 2018;28:745–54., - PubMed

[27] (e) Supuran CT, Capasso C. An overview of the bacterial carbonic anhydrases. Metabolites 2017;7:56. - PMC - PubMed

[28] (a) Supuran CT. Carbonic anhydrase inhibitors and activators for novel therapeutic applications. Future Med Chem 2011;3:1165–80., - PubMed

(b) Akocak S, Lolak N, Bua S, et al. . Discovery of novel 1,3-diaryltriazene sulfonamides as carbonic anhydrase I, II, VII, and IX inhibitors. J Enzyme Inhib Med Chem 2018;33:1575–80., - PMC - PubMed

(c) Winum JY, Temperini C, El Cheikh K, et al. . Carbonic anhydrase inhibitors: clash with Ala65 as a means for designing inhibitors with low affinity for the ubiquitous isozyme II, exemplified by the crystal structure of the topiramate sulfamide analogue. J Med Chem 2006;49:7024–31., - PubMed

(d) Supuran CT. Carbonic anhydrase inhibitors in the treatment and prophylaxis of obesity. Expert Opin Ther Pat 2003;13:1545–50.

[29] (a) Supuran CT. Carbonic anhydrase inhibitors and activators for novel therapeutic applications. Future Med Chem 2011;3:1165–80., - PubMed

[30] (b) Akocak S, Lolak N, Bua S, et al. . Discovery of novel 1,3-diaryltriazene sulfonamides as carbonic anhydrase I, II, VII, and IX inhibitors. J Enzyme Inhib Med Chem 2018;33:1575–80., - PMC - PubMed

[31] (c) Winum JY, Temperini C, El Cheikh K, et al. . Carbonic anhydrase inhibitors: clash with Ala65 as a means for designing inhibitors with low affinity for the ubiquitous isozyme II, exemplified by the crystal structure of the topiramate sulfamide analogue. J Med Chem 2006;49:7024–31., - PubMed

[32] (d) Supuran CT. Carbonic anhydrase inhibitors in the treatment and prophylaxis of obesity. Expert Opin Ther Pat 2003;13:1545–50.

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Synthesis and biological evaluation of novel 3-(quinolin-4-ylamino)benzenesulfonamidesAQ3 as carbonic anhydrase isoforms I and II inhibitors

Affiliations

Synthesis and biological evaluation of novel 3-(quinolin-4-ylamino)benzenesulfonamidesAQ3 as carbonic anhydrase isoforms I and II inhibitors

Authors

Affiliations

Abstract

Figures

Similar articles

Cited by

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Abstract

Figures

Similar articles

Cited by

References

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full Text Sources