Tryptanthrin from microwave-assisted reduction of isatin using solid-state-supported sodium borohydride: DFT calculations, molecular docking and evaluation of its analgesic and anti-inflammatory activity

Craig A Obafemi; Oluwaseun B Adegbite; Olatomide A Fadare; Ezekiel O Iwalewa; Nusrat O Omisore; Kayode Sanusi; Yusuf Yilmaz; Ümit Ceylan

doi:10.1016/j.heliyon.2020.e05756

Tryptanthrin from microwave-assisted reduction of isatin using solid-state-supported sodium borohydride: DFT calculations, molecular docking and evaluation of its analgesic and anti-inflammatory activity

Heliyon. 2020 Dec 31;7(1):e05756. doi: 10.1016/j.heliyon.2020.e05756. eCollection 2021 Jan.

Authors

Craig A Obafemi¹, Oluwaseun B Adegbite¹, Olatomide A Fadare¹, Ezekiel O Iwalewa², Nusrat O Omisore³, Kayode Sanusi¹, Yusuf Yilmaz⁴, Ümit Ceylan⁵

Affiliations

¹ Department of Chemistry, Faculty of Science, Obafemi Awolowo University, Ile-Ife, Nigeria.
² Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan; Nigeria.
³ Department of Pharmacology, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria.
⁴ NT Vocational School, Gaziantep University, 27310, Gaziantep, Turkey.
⁵ Department of Medical Services and Techniques, Vocational High School Health Services, Giresun University, 28100, Giresun, Turkey.

Abstract

Tryptanthrin is a potent natural alkaloid with good in vitro pharmacological properties. Herein, we report the synthesis of the compound via a new method involving the reduction of isatin with solid-state-supported sodium borohydride under microwave irradiation. The title compound has been tested for its analgesic and anti-inflammatory activity. The results showed that tryptanthrin dose dependently inhibits oedema and pain formation in all the models used. The agent also exhibited significant higher effects in its anti-inflammatory and analgesic activities better than positive drugs (aspirin and indomethacin) being currently used in the treatment and in the management of acute and chronic forms of pain and inflammatory disorders. The inhibitory potential of the compound was investigated by molecular docking using the software AutoDock Vina. The docking results were used to better rationalize the action and prediction of the binding affinity of tryptanthrin. Density Functional Theory (DFT) calculations at the B3LYP/6-311++G (2df, 2pd) level of theory showed that compared to ascorbic acid, tryptanthrin shows higher antioxidant activity which may be improved upon by functionalizing the aromatic core to enhance its solubility in polar solvents. The calculated electronic and thermodynamic properties obtained for tryptanthrin compete well with the standard ascorbic acid.

Keywords: Analgesic and anti-inflammatory activity; Borohydride reduction; DFT calculations; Isatin; Molecular docking; Tryptanthrin.