چکیده مقاله
Histone deacetylase 8 HDAC8 is highly expressed in hematological malignancies Mostavailable HDAC8 inhibitors possess a hydroxamic acid group, which creates a strong bind withthe zinc ion in HDAC8 However, this high binding affinity can cause severe side effects Moreover, other non selective HDAC8 inhibitors may have adverse effects This study aimed toidentify potential, non hydroxamate, selective, and novel HDAC8 inhibitors A pharmacophorehypothesis AADH 1 and a quantitative structure activity relationship QSAR model weregenerated using 62 well known HDAC8 inhibitors For virtual screening over6×10 4 moleculesin the ZINC database were applied For the 2D QSAR model, R2= 0 9042 for the training setand R2= 0 8186 for the test set were calculated and the pharmacophore modeling was validatedwith approved and investigational HDAC8 inhibitors from DRUGBANK, enhancing itsreliability The resultant hits with a fitness score > 1 75 and predicted IC50 < 80 nm werescreened by ADMET predictions absorption, distribution, metabolism, excretion, and toxicity and docking investigations ZINC00001899, ZINC00188775, ZINC00374103, ZINC02100923, ZINC02769898, ZINC03034178, ZINC08426994, ZINC32559928 have more affinity towards HDAC8 and less affinity towards HDAC3 and HDAC6 ZINC00001899 Penciclovir, used in clinical trials for treating HSV infections, may selectively inhibit HDAC8 with fewer side effects for related disorders
کلیدواژهها
نویسندگان
Ali Salavati
Chemical and Petroleum Engineering Department, Sharif University of Technology, ۱۱۳۶۵‐۹۴۶۵, Tehran, Iran
Ahmad Ramazani S.A
Chemical and Petroleum Engineering Department, Sharif University of Technology, ۱۱۳۶۵‐۹۴۶۵, Tehran, Iran
Seyedeh Mozhdeh Mirzaei
Medical nanotechnology department, Mashhad University of Medical Science, Mashhad, Iran
شیوه ارجاع
Salavati, Ali and Ramazani S.A, Ahmad and Mirzaei, Seyedeh Mozhdeh,1402,A Multi-Method In-Silico Modeling Approach to Discover Novel PotentialSelective HDAC8 Inhibitors for Therapeutic Cancer Studies,the seventh International Conference on Technology Development in Chemical Engineering,Tehran
ارائهشده در
مجموعه مقالات هفتمین کنفرانس بین المللی توسعه فناوری در مهندسی شیمی30 بهمن 1402 · تهران