Structural elucidation, molecular docking, α-amylase and α-glucosidase inhibition studies of 5-amino-nicotinic acid derivatives

Muhammad Nawaz; Muhammad Taha; Faiza Qureshi; Nisar Ullah; Manikandan Selvaraj; Sumaira Shahzad; Sridevi Chigurupati; Abdul Waheed; Fadiah Ammar Almutairi

doi:10.1186/s13065-020-00695-1

Structural elucidation, molecular docking, α-amylase and α-glucosidase inhibition studies of 5-amino-nicotinic acid derivatives

BMC Chem. 2020 Jul 14;14(1):43. doi: 10.1186/s13065-020-00695-1. eCollection 2020 Dec.

Authors

Muhammad Nawaz¹, Muhammad Taha², Faiza Qureshi^{1

3}, Nisar Ullah⁴, Manikandan Selvaraj⁵, Sumaira Shahzad⁶, Sridevi Chigurupati⁷, Abdul Waheed⁴, Fadiah Ammar Almutairi⁷

Affiliations

¹ Department of Nano-Medicine Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam, 31441 Saudi Arabia.
² Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam, 31441 Saudi Arabia.
³ Deanship of Scientific Research, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam, 31441 Saudi Arabia.
⁴ Chemistry Department, King Fahd University of Petroleum & Minerals, Dhahran, 31261 Saudi Arabia.
⁵ School of Chemical Engineering, Monash University, Bandar Subway, 47500 Selangor Darul Ehsan, Malaysia.
⁶ School of Business Administration, College of International Education, Zhejiang Gongshang University, Hangzhou, China.
⁷ Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraidah, 52571 Saudi Arabia.

Abstract

In this study, 5-amino-nicotinic acid derivatives (1-13) have been designed and synthesized to evaluate their inhibitory potential against α-amylase and α-glucosidase enzymes. The synthesized compounds (1-13) exhibited promising α-amylase and α-glucosidase activities. IC₅₀ values for α-amylase activity ranged between 12.17 ± 0.14 to 37.33 ± 0.02 µg/mL ± SEM while for α-glucosidase activity the IC₅₀ values were ranged between 12.01 ± 0.09 to 38.01 ± 0.12 µg/mL ± SEM. In particular, compounds 2 and 4-8 demonstrated significant inhibitory activities against α-amylase and α-glucosidase and the inhibitory potential of these compounds was comparable to the standard acarbose (10.98 ± 0.03 and 10.79 ± 0.17 µg/mL ± SEM, respectively). In addition, the impact of substituent on the inhibitory potential of these compounds was assessed to establish structure activity relationships. Studies in molecular simulations were conducted to better comprehend the binding properties of the compounds. All the synthesized compounds were extensively characterized with modern spectroscopic methods including ¹H-NMR, ¹³C-NMR, FTIR, HR-MS and elemental analysis.

Keywords: 5-Amino-nicotinic acid; FTIR; HR-MS; Molecular docking; NMR; Spectral studies; α-Amylase activity; α-Glucosidase activity.