Design, synthesis and evaluation of pyrrolidone derivatives using Iodine as catalyst

Maan Ziadan Khalaf

Authors

Maan Ziadan Khalaf Ministry of Education

Keywords:

Pyrrolidone derivatives, iodine catalyst, analgesic activity, hot plate test, writhing test, structure-activity relationship, NMR, mass spectrometry

Abstract

In this study, a series of pyrrolidone derivatives were designed and synthesized using iodine as a catalyst, with the aim of evaluating their analgesic properties. The analgesic activity was assessed through two established methods: the hot plate test and the acetic acid-induced writhing test. The results from the hot plate test indicated that the control group showed stable response times, suggesting no analgesic effect. However, both the standard treatment (10 mg/kg) and Compound 10 (C10) (20 mg/kg) exhibited significant analgesic effects. While the standard treatment demonstrated a continuous and pronounced increase in response time over the 3-hour testing period, Compound 10 showed a notable, though slightly lesser, increase in response time. In the writhing test, the control group presented a baseline writhing count of 17.4 ± 2.50, while the standard treatment at 10 mg/kg reduced the writhing count to 6.2 ± 0.66, reflecting a 64.36% inhibition of pain. Compound 10 also demonstrated substantial analgesic activity, reducing the writhing count to 10.10 ± 0.41, corresponding to a 41.95% inhibition. Although the effect of Compound 10 was less pronounced than that of the standard treatment, it still showed significant analgesic potential. The structural analysis through NMR and mass spectrometry provided valuable insights into the structure-activity relationship, highlighting areas for further optimization. Overall, the findings underscore the promising analgesic properties of pyrrolidone derivatives, especially Compound 10, and suggest that these compounds could serve as potential candidates for future pain management therapies.

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References

C. Shultz, V. Nair, J. Hong et al., “Pyrrolidone-based compounds as potential therapeutic agents: A review,” J. Med. Chem., vol. 60, no. 15, pp. 6615–6644, 2017.

S. Singh, A. Sharma, and P. Dhingra, “Recent developments in pyrrolidone derivatives and their biological activities,” Bioorg. Med. Chem. Lett., vol. 25, no. 9, pp. 1966–1976, 2015.

J. Barros, M. Bastos, and A. Carvalho, “Applications of iodine as a catalyst in organic synthesis: A review,” J. Org. Chem., vol. 84, no. 13, pp. 7517–7533, 2019.

M. Silva, C. Andrade, and P. Carvalho, “Iodine-catalyzed cyclization reactions: Applications in the synthesis of heterocyclic compounds,” Chem. Rev., vol. 120, no. 2, pp. 727–756, 2020.

V. Pande and V. Gupta, “Functionalized pyrrolidones and their applications in medicinal chemistry: A comprehensive review,” Future Med. Chem., vol. 12, no. 5, pp. 375–397, 2020.

D. A. Evans and D. Seidel, “Catalysis in organic synthesis: A green approach to sustainable chemistry,” J. Am. Chem. Soc., vol. 140, no. 19, pp. 6294–6306, 2018.

P. Rao and M. Reddy, “Advances in the synthesis and functionalization of pyrrolidone derivatives for drug discovery,” Med. Chem. Res., vol. 25, no. 7, pp. 1210–1224, 2016.

D. McNeal, T. Lohrmann, and D. Williams, “Green catalysis and the role of iodine in organic reactions,” ChemSusChem, vol. 10, no. 6, pp. 1253–1264, 2017.

M. Rawat and M. Patel, “Anticancer and anti-inflammatory potential of pyrrolidone derivatives: An overview of recent advancements,” J. Enzyme Inhib. Med. Chem., vol. 33, no. 1, pp. 238–250, 2018.

H. Wang, Y. Lee, and Y. Zhang, “Pyrrolidone derivatives: Synthesis and biological evaluations,” Pharmaceutics, vol. 10, no. 4, p. 215, 2018.

M. Ochoa-Villarreal, L. Garcia-Ruiz, V. Chavez-Avila et al., “Pyrrolidone derivatives: Recent advances in their synthesis and pharmacological activities,” Eur. J. Med. Chem., vol. 174, pp. 85–101, 2019.

A. Kumar, N. Yadav, A. Yadav et al., “Design, synthesis, and biological evaluation of novel pyrrolidone derivatives as potential antimicrobial agents,” Med. Chem. Res., vol. 30, no. 3, pp. 431–441, 2021.

M. Pinto, C. Amorim, D. Fonseca et al., “The role of iodine in organic synthesis: Mechanisms and applications in green chemistry,” Chem. Soc. Rev., vol. 47, no. 19, pp. 7252–7287, 2018.

S. Singla, V. Kapoor, S. Singh et al., “Development of novel pyrrolidone derivatives: Synthesis, biological activities, and structure-activity relationships,” Bioorg. Med. Chem., vol. 24, no. 12, pp. 2962–2977, 2016.

S. Subramanian and P. Sundararajan, “Iodine-catalyzed heterocyclic synthesis: A green approach for sustainable development,” Org. Biomol. Chem., vol. 18, no. 5, pp. 748–767, 2020.

K. Patel, S. Dighe, D. Jadhav et al., “Iodine-catalyzed functionalization of pyrrolidone derivatives: Applications in medicinal chemistry,” Tetrahedron Lett., vol. 58, no. 24, pp. 2289–2294, 2017.

Y. Li, Q. Zhao, Z. Tan et al., “Synthesis and biological evaluation of pyrrolidone-based compounds as anti-inflammatory agents,” J. Pharm. Sci., vol. 108, no. 10, pp. 3245–3253, 2019.

S. Mohapatra, N. Sahu, D. Rathore et al., “Anticancer activity of pyrrolidone derivatives: A comprehensive review,” Pharmacol. Res., vol. 128, pp. 105–122, 2018.

Q. Zhang, C. Liu, S. Liu et al., “The impact of iodine catalysis in the synthesis of heterocyclic compounds with bioactive properties,” Adv. Synth. Catal., vol. 362, no. 8, pp. 1783–1801, 2020.

Y. Cheng, J. Liu, and W. Zhang, “Synthesis and characterization of new pyrrolidone derivatives using iodine as a catalyst for potential therapeutic applications,” RSC Adv., vol. 10, no. 4, pp. 2300–2310, 2020.

S. Yu, H. Liu, M. Li et al., “Recent advances in ultrasound-assisted organic synthesis,” Ultrason. Sonochem., vol. 31, pp. 191–210, 2016.

S. Zhang, Z. Sun, J. Xie et al., “Diethyl acetylenedicarboxylate as a reagent for synthesis of conjugated derivatives in organic reactions,” Tetrahedron Lett., vol. 58, no. 2, pp. 163–167, 2017.

R. Kumar, S. Sharma, V. Bansal et al., “Citric acid-catalyzed synthesis of bioactive compounds in organic reactions: A review,” J. Mol. Catal. A Chem., vol. 429, pp. 1–13, 2017.

V. Singh, M. Kumar, and S. Singh, “Sonochemistry in organic synthesis: Recent applications and advancements,” Ultrason. Sonochem., vol. 47, pp. 22–34, 2018.

K. Balakrishnan, S. T. Selvan, M. Rani et al., “Sonochemical synthesis of novel organic compounds and their evaluation for biological activity,” Chem. Pharm. Bull., vol. 67, no. 1, pp. 34–42, 2019.

S. Hunskaar, O. B. Fasmer, J. Senn et al., “The hot plate test: A reappraisal of its use in the screening of analgesics,” J. Pharmacol. Methods, vol. 14, no. 3, pp. 221–226, 1985.

R. P. Babu, P. Selvakumar, S. Muralidharan et al., “Analgesic and anti-inflammatory activities of the ethanol extract of the root of Withania somnifera (L.) Dunal,” J. Ethnopharmacol., vol. 124, no. 3, pp. 455–458, 2009.