Synthesis, characterization, crystal structure and bioactivities of 
novel enamine and pyrrole derivatives endowed with 
acetylcholinesterase, α-glycosidase and human carbonic 
anhydrase inhibition effects

Demir, Yeliz; Gulcin, ilhami; Abel, Maharramov; Safarova, Ayten; Kurbanova, Malahat; Taslimi, Parham; Alwasel, Saleh; Sujayev, Afsun; Huseynov, Elnur

doi:10.25135/acg.oc101.21.04.2029

Synthesis, characterization, crystal structure and bioactivities of novel enamine and pyrrole derivatives endowed with acetylcholinesterase, α-glycosidase and human carbonic anhydrase inhibition effects

Abel MAHARRAMOV, (Baku State University, Organic Chemistry Department, Z. Khalilov, Baku, Azerbaijan)

Malahat KURBANOVA, (Baku State University, Organic Chemistry Department, Z. Khalilov, Baku, Azerbaijan)

Parham TASLİMİ, (Bartın Üniversitesi, Fen Fakültesi, Biyoteknoloji Bölümü, Bartın, Türkiye)

Yeliz DEMİR, (Ardahan Üniversitesi, Nihat Delibalta Göle Meslek Yüksek Okulu, Eczacılık Hizmetleri Bölümü, Ardahan, Türkiye)

Aytan SAFAROVA, (Baku State University, Organic Chemistry Department, Z. Khalilov, Baku, Azerbaijan)

Elnur HUSEYİNOV, (Baku State University, Organic Chemistry Department, Z. Khalilov, Baku, Azerbaijan)

Afsun SUJAYEV, (Baku State University, Organic Chemistry Department, Z. Khalilov, Baku, Azerbaijan)

Saleh H. ALWASEL, (King Saud University, College of Science, Department of Zoology, Riyadh, Saudi Arabia)

İlhami GÜLÇİN (Atatürk Üniversitesi, Fen Fakültesi, Kimya Bölümü, Erzurum, Türkiye)

Organic Communications

11 0

Yıl: 2021 Cilt: 14 Sayı: 2 Sayfa Aralığı: 144 - 156 Metin Dili: İngilizce DOI: 10.25135/acg.oc101.21.04.2029 İndeks Tarihi: 27-06-2022

Synthesis, characterization, crystal structure and bioactivities of novel enamine and pyrrole derivatives endowed with acetylcholinesterase, α-glycosidase and human carbonic anhydrase inhibition effects

Öz:

Presented research work is devoted to the synthesis of new heterocyclic compounds containing the ethyl ester fragment of acetate and glycine and the study of their crystal structure and biological activity. (Z)-Ethyl 2-(3- oxo-1,3-diphenylprop-1-enylamino)acetate (1) was first obtained on the base of the reaction of dibenzene methane with glycine ethyl ester hydrochloride in the presence of Y(OTF)3 catalyst in aqueous medium. At the same time, ethyl-3,5-diphenyl-1H-pyrrole-2-carboxylate (2) was synthesized from the interaction of enamine with tert-BuOK in the presence of tert-BuOH/DMFA solvent. The structure of new compounds has been studied by 1H, 13C NMR. In addition, the crystal structure of ethyl-3,5-diphenyl-1H-pyrrole-2-carboxylate (2) is presented. The monoclinic, yellow crystals, with sizes 0.20 × 0.10 × 0.10 mm3 , one striped: a = 10.5340(6) Е, b = 7.5101(5) Е, c = 20.2352(15) Å, β = 102.131(2)°, V = 1565.09(18) Е3 , space group P21/c, Z= 4, ds = 1.236 mg/m3 , μ = 0.080 mm-1 were obtained. The crystalline compound keeps crystallographically independent molecules in the central bicyclic moiety. Compound 2 holds complex three-organic compound system consisting of pyrrole and benzol rings. In this study, the IC50 and Ki values of the compounds were calculated to compare their inhibition profiles on acetylcholinesterase (AChE), α-glycosidase and hCA I, and II isozymes. These compounds demonstrated Ki values in the low micromolar range for studied enzymes. The best inhibitor for hCA I and II isoenzymes and AChE was the (1) with Ki values of 47.21±5.06, 35.77±3.53 and 103.94±15.36 µM, respectively. On the other hand, compound 2 showed the best inhibition profile against α-glycosidase with Ki of 63.76±7.12 µM.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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[84] Garibov, E.; Taslimi, P.; Sujayev, A.; Bingöl, Z.; Çetinkaya, S.; Gulcin, I.; Beydemir, S.; Farzaliyev, V.; Alwasel, S.H.; Supuran, C.T. Synthesis of 4,5-disubstituted-2-thioxo-1,2,3,4-tetrahydropyrimidines and investigation of their acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase I/II inhibitory and antioxidant activities. J. Enzyme Inhib. Med. Chem. 2016, 31(S3), 1-9.
[85] Kucukoglu, K.; Oral, F.; Aydin, T.; Yamali, C.; Algul, O.; Sakagami, H.; Gulcin, I.; Supuran, C.T.; Gul, H.I. Synthesis, cytotoxicity and carbonic anhydrase inhibitory activities of new pyrazolines. J. Enzyme Inhib. Med. Chem. 2016, 31(S4): 20-24.
[86] Gulcin, I.; Trofimov, B.; Kaya, R.; Taslimi, P.; Sobenina, L.; Schmidt, E.; Petrova, O.; Malysheva, S.; Gusarova, N.; Farzaliyev V.; Sujayev A.; Alwasel S, Supuran C.T. Synthesis of nitrogen, phosphorus, selenium and sulfur-containing heterocyclic compounds-determination of their carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase and α-glucosidase ınhibition properties. Bioorg. Chem. 2020, 103, 104171.
[87] Okten, S.; Aydın, A.; Koçyiğit, U.M.; Çakmak, O.; Erkan, S.; Andac, C.A.; Taslimi, P.; Gulcin, I. Quinolinebased promising anticancer and antibacterial agents, and some metabolic enzymes inhibitors. Arch. Pharm. 2020, 353(9), e2000086.
[88] Dasgin, S.; Gok, Y.; Barut Celepci, D.; Taslimi, P.; İzmirli, M.; Aktaş, A.; Gulçin, İ. Synthesis, characterization, crystal structure and bioactivity properties of the benzimidazole-functionalized PEPPSI type of Pd(II)NHC complexes. J. Mol. Struct. 2020, 1228, 129442.
[89] Yamali, C.; Gül, H.I.; Demir, Y.; Kazaz, C.; Gulcin, I. Synthesis and bioactivities of 1-(4-hydroxyphenyl)- 2-((heteroaryl)thio)ethanones as carbonic anhydrase I, II and acetylcholinesterase inhibitors. Turk. J. Chem. 2020, 44, 1058-1067.
[90] Gul, H.I.; Mete, E.; Taslimi, P.; Gulcin, I.; Supuran, C.T. Synthesis, carbonic anhydrase I and II inhibition studies of the 1,3,5-trisubstituted-pyrazolines. J. Enzyme Inhib. Med. Chem. 2017, 32, 189-192.
[91] Aktaş, A.; Celepci, D.B.; Kaya, R.; Taslimi, P.; Gök, Y.; Aygün, M.; Gulcin, I. Novel morpholine liganded Pd-based N-heterocyclic carbene complexes: Synthesis, characterization, crystal structure, antidiabetic and anticholinergic properties. Polyhedron, 2019, 159, 345-354.
[92] Erdemir, F.; Barut, Celepci, D.; Aktas, A.; Gök, Y.; Kaya, R.; Taslimi, P.; Demir, Y.; Gulcin, I. Novel 2- aminopyridine liganded Pd(II) N-heterocyclic carbene complexes: synthesis, characterization, crystal structure and bioactivity properties. Bioorg. Chem. 2019, 91, 103134.
[93] Isık, M.; Akocak, S.; Lolak, N.; Taslimi, P.; Turkes, C.; Gulcin, I.; Durgun, M.; Beydemir, S. Synthesis, characterization, biological evaluation, and in silico studies of novel 1,3-diaryltriazene-substituted sulfathiazole derivatives. Arch. Pharm. 2020, 353(9), e2000102.
[94] Demir, Y.; Taslimi, P.; Ozaslan, M.S.; Oztaskın, N.; Çetinkaya, Y.; Gulcin, I.; Beydemir, S.; Göksu, P. Antidiabetic potential: In vitro inhibition effects of bromophenol and diarylmethanones derivatives on metabolic enzymes. Arch. Pharm. 2018, 351(12), e1800263.
[95] Bal, S.; Demirci, Ö.; Aktaş, A.; Şen, B.; Taslimi, P.; Aktaş, A.; Gök, Y.; Aygün, M.; Gulçin, İ. PEPPSI type Pd(II)NHC complexes bearing Chloro-/Fluorobenzyl group: Synthesis, characterization, crystal structures, α-glycosidase and acetylcholinesterase inhibitory properties. Polyhedron, 2021, 198, 115060.
[96] Günsel, A.; Yaşa Atmaca, G, Taslimi, P.; Bilgiçli, A.T.; Gulçin, İ.; Erdoğmuş, A.; Yaraşır, M.N. Synthesis, characterization, photo-physicochemical and biological properties of water-soluble tetra-substituted phthalocyanines: Antidiabetic, anticancer and anticholinergic potentials. J. Photoch. Photobiol. A 2020, 396, 112511.
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[99] Bursal, E.; Aras, A.; Kılıç, Ö.; Taslimi, P.; Gören, A.C.; Gulcin, I. Phytochemical content, antioxidant activity, and enzyme inhibition effect of Salvia eriophora Boiss. & Kotschy against acetylcholinesterase, αamylase, butyrylcholinesterase, and α-glycosidase enzymes. J. Food Biochem. 2019, 43(3), e12776.
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[101] Demir, Y.; Duran, H.E.; Durmaz, L.; Taslimi, P.; Beydemir, S.; Gulcin, I. The influence of some nonsteroidal anti-inflammatory drugs on metabolic enzymes of aldose reductase, sorbitol dehydrogenase, and a-glycosidase: A perspective for metabolic disorders. Appl. Biochem. Biotechnol. 2020, 190(2), 437- 447.
[102] Fatah, N.H.A.; Amen, Y.; Abdel Bar, F.M.; Halim, A.F.; Saad, H.E.A. (2020). Antioxidants and αglucosidase ınhibitors from Lactuca serriola L. Rec. Nat. Prod. 2020, 14(6), 410-415.
[103] Cağlayan, C.; Taslimi, P.; Demir, Y.; Küçükler, S.; Kandemir, M.F.; Gulcin, I. The effects of zingerone against vancomycin‐induced lung, liver, kidney and testis toxicity in rats: The behavior of some metabolic enzymes. J. Biochem. Mol. Toxicol. 2019, 33(10), e22381.
[104] Taslimi, P.; Koksal, E.; Gören, A.C.; Bursal, E.; Aras, A.; Kılıç, O.; Alwasel, S.; Gulcin, I. Anti-Alzheimer, antidiabetic and antioxidant potential of Satureja cuneifolia and analysis of ıts phenolic contents by LCMS/MS. Arab. J. Chem. 2020, 13(3), 4528-4537.
[105] Günsel, A.; Bilgiçli, A.T.; Barut, B.; Taslimi, P.; Ozel, A.; Gulcin, I.; Bıyıklıoglu, Z.; Yarasir, M.N. Synthesis of water soluble tetra-substituted phthalocyanines: Investigation of DNA cleavage, cytotoxic effects and metabolic enzyme inhibition. J. Mol. Struct. 2020, 214, 128210.
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APA	Abel M, Kurbanova M, Taslimi P, Demir Y, Safarova A, Huseynov E, Sujayev A, Alwasel S, Gulcin i (2021). Synthesis, characterization, crystal structure and bioactivities of novel enamine and pyrrole derivatives endowed with acetylcholinesterase, α-glycosidase and human carbonic anhydrase inhibition effects. , 144 - 156. 10.25135/acg.oc101.21.04.2029
Chicago	Abel Maharramov,Kurbanova Malahat,Taslimi Parham,Demir Yeliz,Safarova Ayten,Huseynov Elnur,Sujayev Afsun,Alwasel Saleh,Gulcin ilhami Synthesis, characterization, crystal structure and bioactivities of novel enamine and pyrrole derivatives endowed with acetylcholinesterase, α-glycosidase and human carbonic anhydrase inhibition effects. (2021): 144 - 156. 10.25135/acg.oc101.21.04.2029
MLA	Abel Maharramov,Kurbanova Malahat,Taslimi Parham,Demir Yeliz,Safarova Ayten,Huseynov Elnur,Sujayev Afsun,Alwasel Saleh,Gulcin ilhami Synthesis, characterization, crystal structure and bioactivities of novel enamine and pyrrole derivatives endowed with acetylcholinesterase, α-glycosidase and human carbonic anhydrase inhibition effects. , 2021, ss.144 - 156. 10.25135/acg.oc101.21.04.2029
AMA	Abel M,Kurbanova M,Taslimi P,Demir Y,Safarova A,Huseynov E,Sujayev A,Alwasel S,Gulcin i Synthesis, characterization, crystal structure and bioactivities of novel enamine and pyrrole derivatives endowed with acetylcholinesterase, α-glycosidase and human carbonic anhydrase inhibition effects. . 2021; 144 - 156. 10.25135/acg.oc101.21.04.2029
Vancouver	Abel M,Kurbanova M,Taslimi P,Demir Y,Safarova A,Huseynov E,Sujayev A,Alwasel S,Gulcin i Synthesis, characterization, crystal structure and bioactivities of novel enamine and pyrrole derivatives endowed with acetylcholinesterase, α-glycosidase and human carbonic anhydrase inhibition effects. . 2021; 144 - 156. 10.25135/acg.oc101.21.04.2029
IEEE	Abel M,Kurbanova M,Taslimi P,Demir Y,Safarova A,Huseynov E,Sujayev A,Alwasel S,Gulcin i "Synthesis, characterization, crystal structure and bioactivities of novel enamine and pyrrole derivatives endowed with acetylcholinesterase, α-glycosidase and human carbonic anhydrase inhibition effects." , ss.144 - 156, 2021. 10.25135/acg.oc101.21.04.2029
ISNAD	Abel, Maharramov vd. "Synthesis, characterization, crystal structure and bioactivities of novel enamine and pyrrole derivatives endowed with acetylcholinesterase, α-glycosidase and human carbonic anhydrase inhibition effects". (2021), 144-156. https://doi.org/10.25135/acg.oc101.21.04.2029

APA	Abel M, Kurbanova M, Taslimi P, Demir Y, Safarova A, Huseynov E, Sujayev A, Alwasel S, Gulcin i (2021). Synthesis, characterization, crystal structure and bioactivities of novel enamine and pyrrole derivatives endowed with acetylcholinesterase, α-glycosidase and human carbonic anhydrase inhibition effects. Organic Communications, 14(2), 144 - 156. 10.25135/acg.oc101.21.04.2029
Chicago	Abel Maharramov,Kurbanova Malahat,Taslimi Parham,Demir Yeliz,Safarova Ayten,Huseynov Elnur,Sujayev Afsun,Alwasel Saleh,Gulcin ilhami Synthesis, characterization, crystal structure and bioactivities of novel enamine and pyrrole derivatives endowed with acetylcholinesterase, α-glycosidase and human carbonic anhydrase inhibition effects. Organic Communications 14, no.2 (2021): 144 - 156. 10.25135/acg.oc101.21.04.2029
MLA	Abel Maharramov,Kurbanova Malahat,Taslimi Parham,Demir Yeliz,Safarova Ayten,Huseynov Elnur,Sujayev Afsun,Alwasel Saleh,Gulcin ilhami Synthesis, characterization, crystal structure and bioactivities of novel enamine and pyrrole derivatives endowed with acetylcholinesterase, α-glycosidase and human carbonic anhydrase inhibition effects. Organic Communications, vol.14, no.2, 2021, ss.144 - 156. 10.25135/acg.oc101.21.04.2029
AMA	Abel M,Kurbanova M,Taslimi P,Demir Y,Safarova A,Huseynov E,Sujayev A,Alwasel S,Gulcin i Synthesis, characterization, crystal structure and bioactivities of novel enamine and pyrrole derivatives endowed with acetylcholinesterase, α-glycosidase and human carbonic anhydrase inhibition effects. Organic Communications. 2021; 14(2): 144 - 156. 10.25135/acg.oc101.21.04.2029
Vancouver	Abel M,Kurbanova M,Taslimi P,Demir Y,Safarova A,Huseynov E,Sujayev A,Alwasel S,Gulcin i Synthesis, characterization, crystal structure and bioactivities of novel enamine and pyrrole derivatives endowed with acetylcholinesterase, α-glycosidase and human carbonic anhydrase inhibition effects. Organic Communications. 2021; 14(2): 144 - 156. 10.25135/acg.oc101.21.04.2029
IEEE	Abel M,Kurbanova M,Taslimi P,Demir Y,Safarova A,Huseynov E,Sujayev A,Alwasel S,Gulcin i "Synthesis, characterization, crystal structure and bioactivities of novel enamine and pyrrole derivatives endowed with acetylcholinesterase, α-glycosidase and human carbonic anhydrase inhibition effects." Organic Communications, 14, ss.144 - 156, 2021. 10.25135/acg.oc101.21.04.2029
ISNAD	Abel, Maharramov vd. "Synthesis, characterization, crystal structure and bioactivities of novel enamine and pyrrole derivatives endowed with acetylcholinesterase, α-glycosidase and human carbonic anhydrase inhibition effects". Organic Communications 14/2 (2021), 144-156. https://doi.org/10.25135/acg.oc101.21.04.2029