Synthesis, in vitro Α-Glucosidase, and acetylcholinesterase inhibitory activities of novel Indol-Fused Pyrano[2,3-D]Pyrimidine compounds

  • Bioorg Med Chem Lett. 2023 Nov 24:98:129566. doi: 10.1016/j.bmcl.2023.129566.
Ha Thanh Nguyen  1 ,  Anh Nguyen Tuan  2 ,  Tuyet Anh Dang Thi  3 ,  Ket Tran Van  4 ,  Giang Le-Nhat-Thuy  3 ,  Phuong Hoang Thi  2 ,  Quynh Giang Nguyen Thi  3 ,  Cham Ba Thi  3 ,  Hung Tran Quang  3 ,  Tuyen Van Nguyen  3
Affiliations
  • 1. Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam; Graduate University of Science and Technology, VAST, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam. Electronic address: [email protected].
  • 2. Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam.
  • 3. Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam; Graduate University of Science and Technology, VAST, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam.
  • 4. Graduate University of Science and Technology, VAST, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam; Military Technology Academy, 236 Hoang Quoc Viet, Bac Tu Liem, Hanoi, Vietnam.
PMID: 38008338 DOI: 10.1016/j.bmcl.2023.129566
Abstract

In this study, new indol-fused pyrano[2,3-d]pyrimidines were designed and synthesized. These products were obtained in moderate to good yields and their structures were assigned by NMR, MS, and IR analysis. Afterwards, the biological important of the products was highlighted by evaluating in vitro for α-glucosidase inhibitory activity as well as acetylcholinesterase (AChE) inhibitory activity. Eleven products revealed substantial inhibitory activity against α-glucosidase enzyme, among which, two most potent products 11d,e were approximately 93-fold more potent than acarbose as a standard antidiabetic drug. Besides that, product 11k exhibited good AChE inhibition. The substituents on the 5-phenyl ring, attached to the pyran ring, played a critical role in inhibitory activities. The biological potencies have provided an opportunity to further investigations of indol-fused pyrano[2,3-d]pyrimidines as potential anti-diabetic agents.

Keywords
3-d]pyrimidine; AChE inhibitors; Diabetes mellitus; Indol-fused pyrano[2; Multicomponent-component reaction; α-glucosidase inhibitors.
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