Project's information
| Project's title | Synthesis and biological evaluation of novel heterocyclic compounds |
| Project’s code | DL0000.04/22-24 |
| Research hosting institution | Institute of Chemistry |
| Project leader’s name | Dr. Tran Quang Hung |
| Project duration | 01/01/2022 - 31/12/2025 |
| Project’s budget | 3,000 million VND |
| Classify | Grade A |
| Goal and objectives of the project | - Study on synthesis of novel heterocyclic compounds. |
| Main results | The project has successfully accomplished all its objectives and research contents, achieving the following main results: On Chemical Synthesis: Successfully established efficient synthetic procedures using green/inexpensive catalysts (Fe, Cu) or multicomponent one-pot reactions to create 129 novel heterocyclic compounds (exceeding the registered target) belonging to 5 structural frameworks: Benzo[f]indole, Chromeno[2,3-d]pyrimidine, Indolopyrano[2,3-d]pyrimidine, Carboline, and Imidazopyridine. All compounds were fully characterized by modern spectroscopic methods (NMR, MS). On Biological Evaluation: Screened and identified several compounds with potent activity, notably: • Cytotoxic activity: Chromeno[2,3-d]pyrimidine derivatives (10c, 10l) and BimPy derivatives (32b, 32c) strongly inhibited lung (A549), breast (MCF-7), and liver (HepG2) cancer cell lines with IC₅₀ values ranging from 1.7 – 4.3 µM, comparable to or better than the reference drug Ellipticine. • Enzyme inhibitory activity: Indolopyrano[2,3-d]pyrimidine derivatives (10’d, 10’e) exhibited α-glucosidase inhibitory activity superior to the drug Acarbose, opening up potential applications in diabetes treatment. On Publications and Training: • Published 04 papers in prestigious international SCIE journals (RSC Advances, ChemistrySelect, Bioorg. Med. Chem. Lett.), exceeding the target (03 papers). • Successfully supported the training of 02 Masters, exceeding the target (01 Master). |
| Novelty and actuality and scientific meaningfulness of the results | - Methodology: The project contributed advanced synthetic solutions (domino reactions, oxidative C-H/C-H coupling), allowing for the rapid construction of complex heterocyclic molecular frameworks from simple starting materials, minimizing costs and environmental impact. - Practical Value: The discovery of "hit compounds" with potent and selective inhibitory activity (especially superior α-glucosidase inhibition compared to commercial drugs) provides valuable data for the future development of new drugs for cancer and diabetes treatment. - Provided new and valuable scientific data on the structure-activity relationship (SAR) of the studied heterocyclic classes, serving as a basis for designing and optimizing drug molecules in the future. |
| Products of the project | Scientific papers in referred journals: [1] Ha Thanh Nguyen, Ha Nguyen Van, Phuong Hoang Thi, Tuyet Anh Dang Thi, Giang Le-Nhat-Thuy, Quynh Giang Nguyen Thi, Anh Nguyen Tuan, Cham Ba Thi, Hung Tran Quang, Tuyen Van Nguyen. Synthesis and cytotoxic evaluation of new fluoro and trifluoromethyl substituents containing chromeno[2,3-d]pyrimidines. ChemistrySelect, 2023, 8, e202300227. doi.org/10.1002/slct.202300227. [2] Ha Thanh Nguyen, Anh Nguyen Tuan, Tuyet Anh Dang Thi, Ket Tran Van, Giang Le-Nhat-Thuy, Phuong Hoang Thi, Quynh Giang Nguyen Thi, Cham Ba Thi, Hung Tran Quang, Tuyen Van Nguyen. Synthesis, in vitro α-glucosidase, and acetylcholinesterase inhibitory activities of novel indol-fused pyrano[2,3-d]pyrimidine compounds. Bioorganic & Medicinal Chemistry Letters, 2024, 98, 129566. doi.org/10.1016/j.bmcl.2023.129566. [3] Tran Quang Hung, Ban Van Phuc, Mai Phuong Nguyen, Tuan Linh Tran, Dang Van Do, Ha Thanh Nguyen, Van Tuyen Nguyen, Hien Nguyen, Tuan Thanh Dang. FeBr3-catalysed synthesis of 3-aroylimidazo[1,2-a]pyridine and 3,3’-(arylmethylene)bis(2-phenylimidazo[1,2-a]pyridines) derivatives from 2-arylimidazo[1,2-a]pyridines and aromatic aldehydes: an investigation about mechanistic insights. RSC Advances, 2024, 14, 29535-29541. DOI: 10.1039/d4ra05198j. [4] Tran Quang Hung, Ban Van Phuc, Ha Nam Do, Thu Hue Tran, Hai Yen Nguyen, Nguyen Truong Phuoc, Truong Mai Chi, Dang Van Do, Truong T. T. Nga, Hien Nguyen, Van Tuyen Nguyen, Tuan Thanh Dang. One-pot acid-catalysed synthesis of bis(1-imidazo[1,5-a]pyridyl)arylmethanes and evaluation of cytotoxic activities. RSC Advances, 2025, 15, 4274-4280. DOI: 10.1039/d4ra08868a. Other products: Training: 02 Master's students 1. M.Sc. Nguyen Van Hau successfully defended his thesis and received a Master's degree in Inorganic Chemistry. The degree was issued by the President of Hanoi National University of Education. The thesis title is “Synthesis, structure and properties of some Cu(I, II), Zn(II) complexes with bis(1-imidazo[1,5-a]pyridine)arylmethane derivatives”. Supervisors: Assoc. Prof. Dr. Le Thi Hong Hai, Dr. Tran Quang Hung. 2. M.Sc. Do Ha Nam successfully defended his thesis and received a Master's degree in Chemistry. The degree (No. 045597) was issued by the Rector of VNU University of Science on April 14, 2025 (recorded in certificate book No. 041/25/TN). The thesis title is “DESIGN, SYNTHESIS OF BIS(3-INDOLYL)METHANES AND EVALUATION OF ANTICANCER ACTIVITY”. Supervisor: Dr. Tran Quang Hung. Samples: 129 novel heterocyclic compounds (>95% purity, >10mg quantity) accompanied by a complete set of structural analysis spectra (¹H NMR, ¹³C NMR, HRMS). Reports: • 01 full set of spectra (¹H NMR, ¹³C NMR, HRMS) confirming the structure of 129 synthesized compounds. • 01 report on the evaluation results of cytotoxic activity, α-glucosidase inhibitory activity, and supplementary Acetylcholinesterase (AChE) inhibitory activity. • Final scientific report of the project. |
| Research area | The project's results are directly applied in scientific research at the Institute of Chemistry, VAST, and serve as a basis for proposing further research directions.a |
| Recommendations | It is recommended that VAST continue to support funding for further in-depth research on the mechanism of action (in vivo) and pharmacokinetics of the identified potential compounds. |
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