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

Mohammad M Al-Sanea; Ahmed Elkamhawy; Sora Paik; Silvia Bua; So Ha Lee; Mohamed A Abdelgawad; Eun Joo Roh; Wagdy M Eldehna; Claudiu T Supuran

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

J Enzyme Inhib Med Chem. 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.

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.

MeSH terms

Benzenesulfonamides
Carbon-13 Magnetic Resonance Spectroscopy
Carbonic Anhydrase I / antagonists & inhibitors*
Carbonic Anhydrase II / antagonists & inhibitors*
Carbonic Anhydrase Inhibitors / chemical synthesis*
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / pharmacology*
Humans
Proton Magnetic Resonance Spectroscopy
Spectrometry, Mass, Electrospray Ionization
Structure-Activity Relationship
Sulfonamides / chemical synthesis*
Sulfonamides / chemistry
Sulfonamides / pharmacology*

Substances

Carbonic Anhydrase Inhibitors
Sulfonamides
Carbonic Anhydrase I
Carbonic Anhydrase II

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).