Doan Thanh Hieu

Bio: Doan Thanh Hieu is an academic researcher from Hanoi University. The author has contributed to research in topics: Histone deacetylase & Docking (molecular). The author has an hindex of 2, co-authored 4 publications receiving 28 citations.

Quinazoline-Based Hydroxamic Acids: Design, Synthesis, and Evaluation of Histone Deacetylase Inhibitory Effects and Cytotoxicity

Abstract: In our search for novel histone deacetylases inhibitors, we have designed and synthesized a series of novel hydroxamic acids and N-hydroxybenzamides incorporating quinazoline heterocycles (4a - 4i, 6a - 6i). Bioevaluation showed that these quinazoline-based hydroxamic acids and N-hydroxybenzamides were potently cytotoxic against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung). In term of cytotoxicity, several compounds, e.g., 4g, 4c, 4g - 4i, 6c, and 6h, displayed from 5- up to 10-fold higher potency than SAHA (suberoylanilidehydroxamic acid, vorinostat). The compounds were also generally comparable to SAHA in inhibiting HDACs with IC50 values in sub-micromolar range. Some compounds, e.g., 4g, 6c, 6e, and 6h, were even more potent HDAC inhibitors compared to SAHA in HeLa extract assay. Docking studies demonstrated that the compounds tightly bound to HDAC2 at the active binding site with binding affinities higher than that of SAHA. Detailed investigation on the estimation of absorption, distribution, metabolism, excretion, and toxicity (ADMET) suggested that compounds 4g, 6c, and 6g, while showing potent HDAC2 inhibitory activity and cytotoxicity, also potentially displayed ADMET characteristics desirable to be expected as promising anticancer drug candidates.

Synthesis and Evaluation of Biological Activities of a Series of (6-substitutedbenzothiazol-2-yl)acrylamides

Abstract: A series of simple (6-substitutedbenzothiazol-2-yl)acrylamides was synthesized and evaluated for cytotoxicity and antimicrobial effects. All six compounds displayed very significant cytotoxicity against four cancer cell lines tested including A549 (a human lung cancer cell line), Hela (a human ovarian cancer cell line), MCF7 (a human breast cancer cell line), and even MCF7-ADR (adriamycin-resistant human breast cancer cell line), with IC50 values in microgram/ml range and as low as 0.66 μg/ml. The synthesized compounds also exhibited some antifungal effects against Apergillus niger.

HDAC -43H- N- N- Novel N-Hydroxybenzamides or N-Hydroxypropenamides Incorporating Quinazolin-43H-ones as Histone Deacetylase Inhibitors and Anticancer Composition Comprising the Same

Abstract: The present invention relates to novel N-hydroxy benzamides or N-hydroxy propenamides based on quinazoline-4(3H)-ones as histone deacetylase (HDAC) inhibitors and a use thereof. More specifically, a compound according to the present invention has a strong HDAC inhibitory activity, thereby being able to be used as proliferation inhibitors for various cancer cells. Therefore, the compound according to the invention is expected to be able to be developed as an active component of strong anti-cancer drugs.

Quinazoline-Based Hydroxamic Acids: Design, Synthesis, and Evaluation of Histone Deacetylase Inhibitory Effects and Cytotoxicity

Abstract: In our search for novel histone deacetylases inhibitors, we have designed and synthesized a series of novel hydroxamic acids and N-hydroxybenzamides incorporating quinazoline heterocycles (4a - 4i, 6a - 6i). Bioevaluation showed that these quinazoline-based hydroxamic acids and N-hydroxybenzamides were potently cytotoxic against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung). In term of cytotoxicity, several compounds, e.g., 4g, 4c, 4g - 4i, 6c, and 6h, displayed from 5- up to 10-fold higher potency than SAHA (suberoylanilidehydroxamic acid, vorinostat). The compounds were also generally comparable to SAHA in inhibiting HDACs with IC50 values in sub-micromolar range. Some compounds, e.g., 4g, 6c, 6e, and 6h, were even more potent HDAC inhibitors compared to SAHA in HeLa extract assay. Docking studies demonstrated that the compounds tightly bound to HDAC2 at the active binding site with binding affinities higher than that of SAHA. Detailed investigation on the estimation of absorption, distribution, metabolism, excretion, and toxicity (ADMET) suggested that compounds 4g, 6c, and 6g, while showing potent HDAC2 inhibitory activity and cytotoxicity, also potentially displayed ADMET characteristics desirable to be expected as promising anticancer drug candidates.

Biologically active quinazoline-based hydroxamic acids

Abstract: Molecular hybridization has become a new promising way to treat multifactorial diseases with a single compound that acts on multiple targets. The combination of several functional pharmacophore groups in one molecule can lead to a stronger therapeutic effect due to the ability to bind to several targets and possible synergistic interactions. The concept of multifunctional agents is being actively developed and has already produced some encouraging results. The quinazoline cycle and hydroxamic acids are unique pharmacophore groups that contribute to the structure of drug agents widely used in medical chemistry. The combination of these pharmacophores in one molecule leads to promising new compounds, which has been confirmed by many experimental studies in published literature across the world. Hybrid compounds of hydroxamic acids and the quinazoline cycle are a potential basis for the development of effective drugs used in the complex treatment of oncological, infectious and neurological diseases. This review provides information on the most significant developments in this area and discusses the bioactivity of important agents. Compounds with both linear hydroxamic acids and cyclic acids in which a hydroxamate group is integrated in the quinazoline ring are also covered in this review.