Abstract
A series of coumarin-based trisubstituted methanes (TRSMs) having uracil scaffold was synthesised employing a green, chromatography-free, and a highly efficient sonochemical multicomponent reaction of diverse aldehydes with 1,3-dimethyl-6-aminouracil and 4-hydroxy-coumarin in the presence of a catalytic amount of DABCO at room temperature and tested their anthelmintic efficacy against helminth parasites, Raillietina echinobothrida and Syphacia obvelata. Some of the TRSMs with substituents in the para position of the phenyl ring showed excellent anthelmintic activity in comparison to the commonly used drugs such as albendazole and praziquantel. The docking study revealed the binding interaction of all the optimized compounds with several amino acid residues in the active site of β-tubulin. The compounds showing good docking score with β-tubulin showed comparable anthelmintic activity experimentally as well.
Graphic Abstract
A series of coumarin based trisubstituted methanes (TRSMs) were synthesized and they showed excellent anthelmintic properties in comparison to conventional benzimidazoles.
Similar content being viewed by others
References
Chatterjee K D 1967 In The Parasitology, Protozoology and Helminthology in relation to clinical medicine (Calcutta, India: Sree Saraswaty Press) p. 168
Mali R G and Mehta A A 2008 A Review on Anthelmintic Plants Nat. Prod. Rad. 7 466
Geary T G, Chibale K, Abegaz B, Andrae-Marobela K and Ubalijoro E 2012 A new approach for anthelmintic discovery for humans Trends Parasitol. 28 176
Paveley R A and Bickle QD 2013 Automated imaging and other developments in whole-organism anthelmintic screening Parasite Immunol. 35 302
Moser W, Schindler C and Keiser J 2017 Efficacy of recommended drugs against soil transmitted helminths: systematic review and network meta-analysis BMJ 358 j4307
Keiser J and Utzinger J 2010 The drugs we have and the drugs we need against major helminth infections Adv. Parasitol. 3 197
Behnke J M, Buttle D J, Stepek G, Lowe A and Duce I R 2008 Developing novel anthelmintics from plant cysteine proteinases Parasit. Vectors 1 29
Silveira C C, Mendes S R, Villetti M A, Backa D F and Kaufman T S 2012 CeIII-promoted oxidation. Efficient aerobic one-pot eco-friendly synthesis of oxidized bis(indol-3-yl)methanes and cyclic tetra(indolyl)dimethanes Green Chem. 1 2912
Srivastava A K, Sharma R, Mishra R, Balapure A K, Murthy P S R and Panda G 2006 Substituted phenanthrenes with basic amino side chains: a new series of anti-breast cancer agents Bioorg. Med. Chem. 14 1497
Al-Qawasmeh R A, Lee Y, Cao M Y, Gu X, Vassilakos A, Wright J A and Young A 2004 Triaryl methane derivatives as antiproliferative agents Bioorg. Med. Chem. Lett. 14 347
Kumar A, Panda G and Siddiqi M I 2007 CoMFA and CoMSIA 3D-QSAR analysis of diaryloxy-methano-phenanthrene derivatives as anti-tubercular agents J. Mol. Model. 13 99
Panda G, Srivastava A K, Parai M K, Das S K, Srivastava A K, Chaturvedi V, Gaikwad A N and Sinha S 2007 Effect of substituents on diarylmethanes for antitubercular activity Eur. J. Med. Chem. 42 410
Tangmouo J G, Meli A L, Komguem J, Kuete V, Ngounou F N, Lontsi D, Beng V P, Choudhary M I and Sondengam B L 2006 Crassiflorone, a new naphthoquinone from Diospyros crassiflora (Hien) Tetrahedron Lett. 47 3067
Yu D, Suzuki M, Xie L, Morris-Natschke S L and Lee K H 2003 Recent progress in the development of coumarin derivatives as potent anti-HIV agents Med. Res. Rev. 23 322
Borges F, Roleira F, Milhazes N, Santana L and Uriarte E 2005 Simple coumarins and analogues in medicinal chemistry: occurrence, synthesis and biological activity Curr. Med. Chem. 12 887
Kraus G A and Kim I 2003 A direct synthesis of O-methyl mlaussequinone J. Org. Chem. 68 4517
Satynarayana V S V, Sreevani P, Sivakumar A and Vijayakumar V 2008 Synthesis and antimicrobial activity of new Schiff bases containing coumarin moiety and their spectral characterization Arkivoc 17 221
Kanth S R, Reddy G V, Kishore K H, Rao P S, Narsaiah B and Murthy U S N 2006 Convenient synthesis of novel 4-substitutedamino-5-trifluoromethyl-2,7-disubstituted pyrido[2,3-d] pyrimidines and their antibacterial activity Eur. J. Med. Chem. 41 1011
Grivsky E M, Lee S, Sigel C W, Duch D S and Nichol C A 1980 Synthesis and antitumor activity of 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine J. Med. Chem. 23 327
Heber D, Heers C and Ravens U 1993 Positive inotropic activity of 5-amino-6-cyano-1,3-dimethyl-1,2,3,4-tetrahydropyrido[2,3-d]pyrim idine-2,4-dione in cardiac muscle from guinea-pig and man. Part 6: Compounds with positive inotropic activity Pharmazie 48 537
Bennett L R, Blankley C J, Fleming R W, Smith R D and Tessman D K 1981 Antihypertensive activity of 6-arylpyrido[2,3-d]pyrimidin-7-amine derivatives J. Med. Chem. 24 382
Davoll J, Clarke J and Elslager E F 1972 Antimalarial substances. 26. Folate antagonists. 4. Antimalarial and antimetabolite effects of 2,4-diamino-6-[(benzyl)amino]pyrido[2,3-d]pyrimidines J. Med. Chem. 15 837
Baruah P, Basumatary, Yesylevskyy S O, Aguan K, Bez G and Mitra S 2019 Novel coumarin derivatives as potent acetylcholinesterase inhibitors: insight into efficacy, mode and site of inhibition J. Biomol. Struct. Dyn. 37 1750
Bharti R and Parvin T 2015 Molecular diversity from the L-proline-catalyzed, three-component reactions of 4-hydroxycoumarin, aldehyde, and 3-aminopyrazole or 1,3-dimethyl-6-aminouracil Synth. Commun. 45 1442
Bharti R and Parvin T 2015 Diversity oriented synthesis of tri-substituted methane containing aminouracil and hydroxynaphthoquinone/hydroxycoumarin moiety using organocatalysed multicomponent reactions in aqueous medium RSC Adv. 5 66833
Ping G and Cai C 2014 A One‐pot, Efficient synthesis of polyfunctionalized pyrido[2,3‐d]pyrimidines and uncyclized adducts by aldehydes, 1,3‐dicarbonyl compounds, and 6‐aminouracils J. Heterocycl. Chem. 51 1595
Bugaut X, Constantieux T, Coquerel Y and Rodriguez J 2014 Multicomponent Reactions in Organic Synthesis J Zhu, Q Wang and M-X Wang (Eds.) (Weinheim: Wiley-VCH) p. 109
Ugi I 2001 Recent progress in the chemistry of multicomponent reactions Pure Appl. Chem. 73 187
Nair V, Rajesh C, Vinod A, Bindu U S, Streekenth A R, Mathen J S and Balagopal L 2003 Strategies for Heterocyclic Construction via Novel Multicomponent Reactions Based on Isocyanides and Nucleophilic Carbenes Acc. Chem. Res. 36 899
Ramon D J and Yus M 2005 Asymmetric Multicomponent Reactions Angew. Chem., Int. Ed. 44 1602
Cravotto G and Cintas P 2006 Power ultrasound in organic synthesis: moving cavitational chemistry from academia to innovative and large-scale applications Chem. Soc. Rev. 35 180
Saleh T S and Abd EL-Rahman N M 2009 Ultrasound promoted synthesis of substituted pyrazoles and isoxazoles containing sulphone moiety Ultrason. Sonochem. 16 237
Mokhtar M, Saleh T S, Ahmed N S, Al-Thabaiti S A and Al-Shareef R A 2011 Ultrasound-assisted synthesis of 2,5-dimethyl-N-substituted pyrroles catalyzed by uranyl nitrate hexahydrate Ultrason Sonochem. 18 172
Vijaya and Yadav A K 2016 In vitro anthelmintic assessment of selected phytochemicals against Hymenolepis diminuta, a zoonotic tapeworm J. Parasit. Dis. 40 1082
Mahmoodi N O, Pirbasti F G and Jalalifard Z 2018 Recent Advances in the Synthesis of Biscoumarin Derivatives J. Chin. Chem. Soc. 65 383
Bihani M, Bora P P, Bez G and Askari H 2014 A green four-component synthesis of zwitterionic alkyl/benzyl pyrazolyl barbiturates and their photophysical studies Mol. Divers. 18 745
Bihani M, Bora P P, Askari H and Bez G 2014 Cooperative catalysis of silica gel with physisorbed water in the synthesis of bis(indolyl)alkanes Ind. J. Chem. 53B 877
Satyendra R V, Vishnumurthy K A and Vagdevi H M 2015 Synthesis, in vitro anthelmintic, and molecular docking studies of novel 5-nitro benzoxazole derivatives Med. Chem. Res. 24 1342
Kohler P and Bachmann R 1981 Intestinal tubulin as possible target for chemotherapeutic action of mebendazole in parasitic nematodes Mol. Biochem. Parasitol. 4 325
Lacey E 1988 The role of the cytoskeletal protein, tubulin, in the mode of action and mechanism of drug resistance to benzimidazoles Int. J. Parasitol. 18 885
Friedman P A and Platzer E G 1978 Interaction of anthelmintic benzimidazoles and benzimidazole derivatives with bovine brain tubulin Biochim. Biophys. Acta 544 605
Funding
This research did not receive any specific grant from funding agency in the public, commercial, or not-for-profit sectors.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of Interest
The authors declare no conflict of interest.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Basumatary, G., Dhar, E.D., Das, D. et al. Coumarin-based Trisubstituted Methanes as Potent Anthelmintic: Synthesis, Molecular Docking and in vitro Efficacy. J Chem Sci 132, 40 (2020). https://doi.org/10.1007/s12039-020-1737-z
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1007/s12039-020-1737-z