Biopolym. Cell. 2020; 36(1):47-59.
Bioorganic Chemistry
Preliminary evaluation of thiazolidinone- and pyrazoline-related heterocyclic derivatives as potential antimalarial agents
1Kryshchyshyn-Dylevych A. P., 1Zelisko N. I., 2Grellier P., 1Lesyk R. B.
  1. Danylo Halytsky Lviv National Medical University
    69, Pekarska Str., Lviv, Ukraine, 79010
  2. National Museum of Natural History, UMR 7245 CNRS MCAM, Sorbonne Universités
    CP 52, 57 Rue Cuvier, Paris 75005, France

Abstract

Aim. Synthesis of a series of thiazolidinone- and pyrazoline-related compounds. In vitro screening of antiplasmodial activity of versatile heterocyclic derivatives. Methods: organic wet synthesis, analytical and spectral methods, pharmacological screening, SAR analysis. Results. A series of different thiazolidinone- and pyrazoline-based derivatives was screened against Plasmodium falciparum in in vitro assays. 5-(Z)-Arylidene-2-arylidenehydrazono-3-(4-hydroxyphenyl)-4-thiazolidinones showed high growth inhibition rates with the IC50–2.32-2.39 µM. 5-Bromo-1-[2-[3-(4-chlorophenyl)-5-(4-methoxyphenyl)-3,4-dihydropyrazol-2-yl]-2-oxoethyl]indoline-2,3-dione 3 was the most active compound among tested with the IC50–1.81 µM. Based on the screening data some structure-activity relationships were derived. Conclusions. A set of different thiazolidinone- and pyrazoline-related derivatives with antitrypanosomal and anticancer properties was screened against Plasmodium falciparum. Hit-compounds inhibiting growth of the parasite at micromolar concentrations were identified. The obtained results provide further avenues to develop more potent antimalarial agents on the base of investigated classes of small drug-like molecules.
Keywords: thiazolidinone, pyrazoline, antimalarial activity, SAR analysis

References

[1] Lesyk R, Zimenkovsky B, Kaminskyy D, Kryshchyshyn A, Havryluk D, Atamanyuk D, Subtel'na I, Khyluk D. Thiazolidinone motif in anticancer drug discovery. Experience of DH LNMU medicinal chemistry scientific group. Biopolym Cell. 2011; 27(2):107-117.
[2] Kaminskyy D, Kryshchyshyn A, Lesyk R. 5-Ene-4-thiazolidinones e an efficient tool in medicinal chemistry. Eur J Med Chem. 2017; 140:542-594.
[3] Kaminskyy D, Kryshchyshyn A, Lesyk R. Recent developments with rhodanine as a scaffold for drug discovery. Expert Opin Drug Discov. 2017; 12:1233-1252.
[4] Kaminskyy D, Subtel'na I, Zimenkovsky B, Karpenko O, Gzella A, Lesyk R. Synthesis and evaluation of anticancer activity of 5-ylidene-4-aminothiazol-2(5H)-one derivatives. Med Chem. 2015; 11:517-530.
[5] Lima Leite A, de M. Moreira D, de O. Cardoso M, Hernandes M, Alves Pereira V, Silva R, Kiperstok A, da S. Lima M, Soares M. Synthesis, cruzain docking, and in vitro studies of aryl-4-oxothiazolylhydrazones against try-panosoma cruzi. Chem Med Chem: Chemistry Enabling Drug Discovery. 2007; 2(9):1339-1345.
[6] Kryshchyshyn A, Kaminskyy D, Grellier P, Lesyk R. Trends in research of antitrypanosomal agents among synthetic heterocycles. Eur J Med Chem. 2014; 85:51-64.
[7] Smith T, Young B, Denton H, Hughes D, Wagner G. First small molecular inhibitors of T. brucei dolicholphos-phate mannose synthase (DPMS), a validated drug target in African sleeping sickness. Bioorg Med Chem Lett. 2009; 19:1749-1752.
[8] Havrylyuk D, Zimenkovsky B, Vasylenko O, Day C, Smee D, Grellier P, Lesyk R. Synthesis and biological activity evaluation of 5-pyrazoline substituted 4-thiazolidinones. Eur J Med Chem. 2013; 66:228-237.
[9] Havrylyuk D, Zimenkovsky B, Karpenko O, Grellier P, Lesyk R. Synthesis of pyrazoline-thiazolidinone hybrids with trypanocidal activity. Eur J Med Chem. 2014; 85:245-254.
[10] Holota S, Kryshchyshyn A, Derkach H, Trufin Y, Demchuk I, Gzella A, Grellier P, Lesyk, R. Synthesis of 5-enamine-4-thiazolidinone derivatives with trypanocidal and anticancer activity. Bioorg Chem. 2019; 86:126-136.
[11] Kryshchyshyn A, Kaminskyy D, Karpenko O, Gzella A, Grellier P, Lesyk R. Thiazolidinone/thiazole based hybrids - New class of antitrypanosomal agents. Eur J Med Chem. 2019; 174:292-308.
[12] Blasco B, Leroy D, Fidock D. Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic. Nat Med. 2017; 23(8):917.
[13] Sharma M, Chauhan K, Srivastava R, Singh S, Srivastava K, Saxena J, Sunil K, Chauhan P. Design and synthesis of a new class of 4-aminoquinolinyl- and 9-anilinoacridinyl schiff base hydrazones as potent antimalarial agents. Chem Biol Drug Des. 2014; 84(2):175-181
[14] Burrows J, Burlot E, Campo B, Cherbuin S, Jeanneret S, Leroy D, Spangenberg T, Waterson D, Wells T, Willis, P. Antimalarial drug discovery-the path towards eradication. Parasitology. 2014; 141(1):128-139.
[15] Branowska D, Farahat A, Kumar A, Wenzler T, Brun R, Liu Y,Wilson D, Boykin D. Synthesis and antiprotozoal activity of 2,5-bis[amidinoaryl]thiazoles. Bioorg Med Chem. 2010; 18(10):3551-3558.
[16] González D, Douelle D, Feng T, Nchinda A, Younis Ya, White K, Wu Q, Ryan E, Burrows J, Waterson D, Witty M, Wittlin S, Charman S, Chiballe K. Novel orally active antimalarial thiazoles. J Med Chem. 2011; 54(21):7713-7719.
[17] Makam P, Thakur P, Kannan, T. In vitro and in silico antimalarial activity of 2-(2-hydrazinyl) thiazole deriva-tives. Eur J Pharm Sci. 2014; 52:138-145.
[18] Hameed P, Chinnapattu M, Shanbag G, Manjrekar P, Koushik K, Raichurkar A, Patil V, Jatheendranath S, Rudrapatna S, Barde S, Rautela N, Awasthy D, Morayya S, Narayan C, Kavanagh S, Saralaya R, Bharath S, Viswanath P, Mukherjee K, Bandodkar B, Srivastava A, Panduga V, Reddy J, Prabhakar K, Sinha A, Jiménez-Díaz M, Martínez M, Angulo-Barturen I, Ferrer S, Sanz L, Gamo F, Duffy S, Avery V, Pamela A. Magistrado P, Lukens A, Wirth D, Waterson D, Balasubramanian V, Iyer P, Shridhar N, Hosagrahara V, Sambandamurthy V, Ramachandran S. Aminoazabenzimidazoles, a novel class of orally active antimalarial agents. J Med Chem. 2014; 57(13):5702-5713.
[19] Kuhen K, Chatterjee A, Rottmann M, Gagaring K, Borboa R, Buenviaje J, Chen Zh, Francek C, Wu T, Nagle A, Barnes W, Plouffe D, Lee M, Fidock D, Graumans W, Vegte-Bolmer M, van Gemert G, Wirjanata G, Sebayang B, Marfurt J, Russell B, Suwanarusk R, Price R, Nosten F, Tungtaeng A, Gettayacamin M, Sattabongkot J,n,k Taylor J, Walker J, Tully D, Patra K, Flannery E, Vinetz J, Renia L, Sauerwein R, Winzeler E, Glynne R, Diagana T. KAF156 is an antimalarial clinical candidate with potential for use in prophylaxis, treatment, and prevention of disease transmission. Antimicrob Agents Chemother. 2014; 58:5060-5067.
[20] Chakka S, Kalamuddin M, Sundararaman S, Wei L, Mundra S, Mahesh R, Malhotra P, Mohmmed A, Kotra L. Identification of novel class of falcipain-2 inhibitors as potential antimalarial agents. Bioorg Med Chem. 2015; 23(9):2221-40.
[21] White N, Pukrittayakamee S, Phyo A, Rueangwee-rayut R, Nosten F, Jittamala P, Jeeyapant A, Jain J, Lefèvre G, Li R, Magnusson B, Diagana T, Leong J. Spiroindolone KAE609 for falciparum and vivax malaria. N Engl J Med. 2014; 371:403-10.
[22] Vaidya A, Morrisey J, Zhang Zh, Das S, Daly T, Otto T, Spillman N, Wyvratt M, Siegl P, Marfurt J, Wirjanata G, Sebayang B, Price R, Chatterjee A, Nagle A, Stasiak M, Charman S, Angulo-Barturen I, Ferrer S, Jiménez-Díaz M, Martínez M, Gamo F, Avery V, Ruecker A, Delves M, Kirk K, Berriman M, Kortagere S, Burrows J, Fan E, Bergman L. Pyrazoleamide compounds are potent antimalarials that target Na+ homeostasis in intraerythrocytic Plasmodium falciparum. Nat Commun. 2014; 5:5521.
[23] McCarthy J, Lotharius J, Rückle T, Chalon S, Phillips M, Elliott S, Sekuloski S, Griffin P, Ng C, Fidock D, Mar-quart L, Williams N, Gobeau N, Bebrevska L, Rosario M, Marsh K, Möhrle J. Safety, tolerability, pharmacokinetics, and activity of the novel long-acting antimalarial DSM265: a two-part first-in-human phase 1a/1b randomised study. Lancet Infect Dis. 2017; 17:626-635.
[24] Bekhit A, Hassan A, El Razik H, El-Miligy M, El-Agroudy E, Bekhit A. New heterocyclic hybrids of pyrazole and its bioisosteres: design, synthesis and biological evaluation as dual acting antimalarial-antileishmanial agents. Eur J Med Chem. 2015; 94:30-44.
[25] Havrylyuk D, Kovach N, Zimenkovsky B, Vasylenko O, Lesyk R. Synthesis and anticancer activity of isatin-based pyrazolines and thiazolidines conjugates. Arch Pharm. 2011; 344(8):514-522.
[26] Havrylyuk D, Zimenkovsky B, Vasylenko O, Zaprutko L, Gzella A, Lesyk R. Synthesis of novel thiazolone-based compounds containing pyrazoline moiety and evaluation of their anticancer activity. Eur J Med Chem. 2009; 44(4):1396-404.
[27] Trager W, Jensen J. Human malaria parasites in continuous culture. Science. 1976; 193(4254):673-5.
[28] Desjardins R, Canfield C, Haynes J, Chulay J. Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrob Agents Chemother. 1979; 16(6):710-8.
[29] Kryshchyshyn A, Atamanyuk D, Kaminskyy D, Grellier P, Lesyk R. Investigation of anticancer and anti-parasitic activity of thiopyrano[2,3-d]thiazoles bearing norbornane moiety. Biopolym Cell. 2017; 33(3):183-205.
[30] Kaminskyy D, Kryshchyshyn A, Nektegayev I, Vasylenko O, Grellier P, Lesyk R. Isothiocoumarin-3-carboxylic acid derivatives: Synthesis, anticancer and antitrypanosomal activity evaluation. Eur J Med Chem. 2014; 75:57-66.
[31] Kryshchyshyn A, Kaminskyy D, Nektegayev I, Grellier P, Lesyk R. Isothiochromenothiazoles - A class of fused thiazolidinone derivatives with established anticancer activity that inhibits growth of Trypanosoma brucei brucei. Sci Pharm. 2018; 86(4):47.
[32] de Siqueira L, de Moraes G, de Lima Ferreira L, de Melo Rego M, Leite A. Multi-target compounds acting in cancer progression: focus on thiosemicarbazone, thiazole and thiazolidinone analogues. Eur J Med Chem. 2019; 170:237-260.
[33] Bolognesi M, Cavalli A. Multitarget drug discovery and polypharmacology. Chem Med Chem. 2016; 11(12):1190-1192.