Design, Synthesis, Anti-inflammatory Evaluation and In silico Molecular
Docking of Novel Furan-based Derivatives as Potential TNF-α Production
Inhibitors

Satish      Bhoge; Prabal   Pratap   Singh; Deepak      Das; Yakub      Ali; Abhijeet      Dhulap

doi:10.2174/1570180820666230828151523

Abstract

Introduction: Inflammation is the first response and an alarming signal for the onset of chronic disease. Most of the anti-inflammatory drugs available in the market are reported to have undesirable gastrointestinal toxicities. Therefore, it is of urgent significance to develop anti-inflammatory drugs with low toxicity and good efficacy.

Methods: We created a targeted scaffold based on a literature review by combining the different structural characteristics of furan and benzyl amides into a single pharmacophore. A series of eighteen furanbased derivatives (1-18) were designed, synthesized for in vitro and in vivo anti-inflammatory activity. The characterization of synthesized compounds was elucidated by techniques like 1H-NMR, 13C-NMR, FT-IR and MS.

Results: The synthetic compounds were examined through molecular docking studies on TNF-α for probable binding mode and interactions with hydrophilic and hydrophobic pocket of TNF-α in comparison to standard drug (Indomethacin).

Conclusion: When compared to the standard treatment, compounds 18, 15 and 9 displayed a remarkable inhibitory effect on the production of TNF-α and in vivo inflammatory activity with no damage to stomach and reduction of LPO. The compounds 18, 15 and 9 might be a good consideration for potential antiinflammatory agents.

« Previous Next »

[1]
Chyan, Y.J.; Chuang, L.M. Dipeptidyl peptidase-IV inhibitors: An evolving treatment for type 2 diabetes from the incretin concept. Recent Pat. Endocr. Metab. Immune Drug Discov.,  2007, 1(1), 15-24.
 [http://dx.doi.org/10.2174/187221407779814570]

[2]
Nathan, C.; Ding, A. Nonresolving inflammation. Cell,  2010, 140(6), 871-882.
 [http://dx.doi.org/10.1016/j.cell.2010.02.029] [PMID:  20303877]

[3]
Fard, M.T.; Arulselvan, P.; Karthivashan, G.; Adam, S.K.; Fakurazi, S. Bioactive extract from moringa oleifera inhibits the pro-inflammatory mediators in lipopolysaccharide stimulated macrophages. Pharmacogn. Mag.,  2015, 11(4), S556-S563.
 [PMID:  27013794]

[4]
Gan, L.; Zheng, Y.; Deng, L.; Sun, P.; Ye, J.; Wei, X.; Liu, F.; Yu, L.; Ye, W.; Fan, C.; Liu, J.; Zhang, W. Diterpenoid lactones with anti-inflammatory effects from the aerial parts of Andrographis paniculata. Molecules,  2019, 24(15), 2726.
 [http://dx.doi.org/10.3390/molecules24152726] [PMID:  31357563]

[5]
Zelová, H.; Hošek, J. TNF-α signalling and inflammation: Interactions between old acquaintances. Inflamm. Res.,  2013, 62(7), 641-651.
 [http://dx.doi.org/10.1007/s00011-013-0633-0] [PMID:  23685857]

[6]
Graninger, W.; Smolen, J. Treatment of rheumatoid arthritis by TNF-blocking agents. Int. Arch. Allergy Immunol.,  2002, 127(1), 10-14.
 [http://dx.doi.org/10.1159/000048164] [PMID:  11893849]

[7]
Pearce, G.J.; Chikanza, I.C. Targeting tumour necrosis factor in the treatment of rheumatoid arthritis. BioDrugs,  2001, 15(3), 139-149.
 [http://dx.doi.org/10.2165/00063030-200115030-00001] [PMID:  11437680]

[8]
Tsutsumi, S.; Gotoh, T.; Tomisato, W.; Mima, S.; Hoshino, T.; Hwang, H-J.; Takenaka, H.; Tsuchiya, T.; Mori, M.; Mizushima, T. Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis. Cell Death Differ.,  2004, 11(9), 1009-1016.
 [http://dx.doi.org/10.1038/sj.cdd.4401436] [PMID:  15131590]

[9]
Bindu, S.; Mazumder, S.; Bandyopadhyay, U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochem. Pharmacol.,  2020, 180, 114147.
 [http://dx.doi.org/10.1016/j.bcp.2020.114147] [PMID:  32653589]

[10]
Sharma, S.; Kumar, D.; Singh, G.; Monga, V.; Kumar, B. Recent advancements in the development of heterocyclic anti-inflammatory agents. Eur. J. Med. Chem.,  2020, 200, 112438.
 [http://dx.doi.org/10.1016/j.ejmech.2020.112438] [PMID:  32485533]

[11]
Patel, N.R.; Patel, D.V. Synthesis and biological activities of vicinal diaryl furans.Vicinal. Diaryl. Subst. Heterocy; Elsevier, 2018, pp. 221-244.
 [http://dx.doi.org/10.1016/B978-0-08-102237-5.00007-9]

[12]
Haider, S.; Alam, M.S.; Hamid, M.; Umar, S.; Kumar, D.; Nazreen, S. Synthesis of novel amide containing Schiff’s bases of 5-(4-chloro-phenyl)-furan-2-carboxaldehyde: Their in vivo anti-inflammatory, antioxidant and antinociceptive activities with ulcerogenic risk evaluation. J. Rep. Pharma. Sci.,  2018, 7(1), 44-63.

[13]
Pomel, V.; Klicic, J.; Covini, D.; Church, D.D.; Shaw, J.P.; Roulin, K.; Burgat-Charvillon, F.; Valognes, D.; Camps, M.; Chabert, C.; Gillieron, C.; Françon, B.; Perrin, D.; Leroy, D.; Gretener, D.; Nichols, A.; Vitte, P.A.; Carboni, S.; Rommel, C.; Schwarz, M.K.; Rückle, T. Furan-2-ylmethylene thiazolidinediones as novel, potent, and selective inhibitors of phosphoinositide 3-kinase gamma. J. Med. Chem.,  2006, 49(13), 3857-3871.
 [http://dx.doi.org/10.1021/jm0601598] [PMID:  16789742]

[14]
Lin, Z.; Li, H.; Luo, H.; Zhang, Y.; Luo, W. Benzylamine and methylamine, substrates of semicarbazide-sensitive amine oxidase, attenuate inflammatory response induced by lipopolysaccharide. Int. Immunopharmacol.,  2011, 11(8), 1079-1089.
 [http://dx.doi.org/10.1016/j.intimp.2011.03.002] [PMID:  21414430]

[15]
Ali, Y.; Alam, M.S.; Hamid, H.; Husain, A.; Kharbanda, C.; Bano, S.; Nazreen, S.; Haider, S. Attenuation of inflammatory mediators, oxidative stress and toxic risk evaluation of Aporosa lindleyana Baill bark extract. J. Ethnopharmacol.,  2014, 155(3), 1513-1521.
 [http://dx.doi.org/10.1016/j.jep.2014.07.035] [PMID:  25124276]

[16]
Slyvka, N.; Saliyeva, L.; Holota, S.; Khyluk, D.; Tkachuk, V.; Vovk, M. Sulfones of pyridinyloxy-substituted imidazo[2,1-b][1,3]thiazines: Synthesis, anti-inflammatory activity evaluation in vivo and docking studies. Lett. Drug Des. Discov.,  2023, 20(11), 1867-1875.
 [http://dx.doi.org/10.2174/1570180819666220812144409]

[17]
Patel, P.K.; Sahu, J.; Chandel, S.S. A detailed review on nociceptive models for the screening of analgesic activity in experimental animals. Int J Neurol Phys Ther.,  2016, 2(6), 44-50.

[18]
Hamid, I.; Nadeem, H.; Ansari, S.F.; Khiljee, S.; Abbasi, I.; Bukhari, A.; Arif, M.; Imran, M. 2-substituted benzoxazoles as potent anti-inflammatory agents: Synthesis, molecular docking and in vivo anti-ulcerogenic studies. Med. Chem.,  2022, 18(7), 791-809.
 [http://dx.doi.org/10.2174/1573406418666211220125344] [PMID:  34931968]

[19]
Bansal, A.; Bali, A.; Balaini, A. Synthesis and evaluation of substituted aryl thiazoles with antioxidant potential as gastro-sparing anti-inflammatory agents. Lett. Drug Des. Discov.,  2020, 17(12), 1566-1578.
 [http://dx.doi.org/10.2174/1570180817999200706005247]

[20]
Holla, B.S.; Malini, K.V.; Sarojini, B.K.; Poojary, B. A novel three‐component synthesis of triazinothiazolones. Synth. Commun.,  2005, 35(3), 333-340.
 [http://dx.doi.org/10.1081/SCC-200048903]

[21]
He, M.; Li, Y.J.; Shao, J.; Fu, C.; Li, Y.S.; Cui, Z.N. 2,5-Disubstituted furan derivatives containing imidazole, triazole or tetrazole moiety as potent α-glucosidase inhibitors. Bioorg. Chem.,  2023, 131, 106298.
 [http://dx.doi.org/10.1016/j.bioorg.2022.106298] [PMID:  36455481]

[22]
Adelusi, T.I.; Oyedele, A.Q.K.; Boyenle, I.D.; Ogunlana, A.T.; Adeyemi, R.O.; Ukachi, C.D.; Idris, M.O.; Olaoba, O.T.; Adedotun, I.O.; Kolawole, O.E.; Xiaoxing, Y.; Abdul-Hammed, M. Molecular modeling in drug discovery. Inform. Med. Unlocked,  2022, 29, 100880.
 [http://dx.doi.org/10.1016/j.imu.2022.100880]

Rights & Permissions Print Cite

Explore Articles

Open Access

Open Access Articles

DOI https://dx.doi.org/10.2174/1570180820666230828151523	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X

Letters in Drug Design & Discovery

Design, Synthesis, Anti-inflammatory Evaluation and In silico Molecular Docking of Novel Furan-based Derivatives as Potential TNF-α Production Inhibitors

Abstract Play Pause

Abstract