TY  - JOUR
T1  - Virtual screening, Molecular Docking, Molecular Dynamic and ADME of new pyrazole derivatives as anticancer
AU  - Alamiri, Ameer
AU  - Abd Razik, Basma M
AU  - Aldabagh, Noor
PY  - 2025
DA  - September
Y2  - 2024
DO  - 10.33435/tcandtc.1525797
JF  - Turkish Computational and Theoretical Chemistry
JO  - Turkish Comp Theo Chem (TC&TC)
PB  - Koray SAYIN
WT  - DergiPark
SN  - 2587-1722
SP  - 45
EP  - 56
VL  - 9
IS  - 3
LA  - en
AB  - Cancer poses a significant global health challenge, demanding the continuous development of effective treatments. This paper explores the domains of virtual screening, molecular docking, pharmacokinetic, and anti-cancer estimation of cell-cycle inhibitors as new pyrazole derivatives. Cancer, a complex ailment characterized by uncontrolled cell growth and metastasis, necessitates innovative and safer anticancer drugs. Traditional chemotherapy, while a primary treatment option, faces challenges such as drug resistance. This paper focuses on finding the safer and effective treatment for lung cancer, the most prevalent and deadly type. NSCLC (Non-small cell lung cancer) account for about 84% of lung malignancies, with LUAD and LUSC being the predominant subtypes. Despite surgery being a common treatment option for NSCLC, many patients are diagnosed at advanced stages, making radiation and chemotherapy the primary treatment modalities. This paper present emphasizing targeted therapy and the role of epidermal growth factor receptor (EGFR). The study introduces a class of heterocyclic compounds, pyrazole derivatives, explored for their distinctive structures and pharmacological activities against cancer. In silico studies, including molecular docking, molecular dynamics and predictions of ADME of the molecules. The results of the molecular docking studies revealed that all six pyrazole derivatives presented respectable attachment energies with the receptor active pocket as comparing with erlotinib and were expected to have promising activity with EGFR protein.
KW  - In silico studies
KW  - virtual screening
KW  - molecular docking
KW  - MDS
KW  - pyrazole derivatives
KW  - EGFR
CR  - [1]	C. Jin, Y.J. Liang, H. He, L. Fu, Synthesis and antitumor activity of ureas containing pyrimidinyl group, European Journal of Medicinal Chemistry 46 (2011) 429–432.
CR  - [2]	B. Ramaswamy, E. Mrozek, J.P. Kuebler, T. Bekaii-Saab, E.H. Kraut, Phase II trial of pyrazoloacridine (NSC# 366140) in patients with metastatic breast cancer, Investigational New Drugs 29 (2011) 347–351.
CR  - [3]	R.N. Regitha, V. Parthasarathy, N. Balakrishnan, Cancer protective effect of Brassica nigra and role of its chemical constituents, Research Journal of Pharmacy and Technology 14 (2021) 1115–1121.
CR  - [4]	World Health Organization, Available online: http://www.who.int/news-room/fact-sheets/detail/cancer (accessed on 15 November 2018).
CR  - [5]	L.A. Torre, F. Bray, R.L. Siegel, J. Ferlay, J. Lortet‐Tieulent, A. Jemal, Global cancer statistics, 2012, CA: a Cancer Journal for Clinicians 65 (2015) 87–108.
CR  - [6]	J.R. Molina, P. Yang, S.D. Cassivi, S.E. Schild, A.A. Adjei, Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship, Mayo Clinic Proceedings 83 (2008) 584–594.
CR  - [7]	N. Vasan, J. Baselga, D.M. Hyman, A view on drug resistance in cancer, Nature 575 (2019) 299–309.
CR  - [8]	S. Nussbaumer, P. Bonnabry, J.L. Veuthey, S. Fleury-Souverain, Analysis of anticancer drugs: A review, Talanta 85 (2011) 2265–2289.
CR  - [9]	Kucukguzel SG, Kucukguzel I, Tatar E, Rollas S. Recent advances in bioactive pyrazoles. Eur J Med Chem. 2015;97:673-690. Available from: https://www.sciencedirect.com/science/article/pii/S0223523414011015
CR  - [10]	G.M. Patel, J.D. Patel, Single Core Osmotic Pump (SCOP): Development of single layer osmotic controlled release tablet for poorly soluble drug, Journal of Pharmaceutical Technology and Drug Research 4 (2012) 1–9.
CR  - [11]	N.E. Mahdy, A.A.R. Rahman, H.A. Hassan, Cytotoxic drugs safety guidelines: Its effect on awareness and safe handling practices of oncology nurses, IOSR Journal of Nursing and Health Science 6 (2017) 22–33.
CR  - [12]	K. Ortiz-Ibáñez, M.M. Alsina, C. Muñoz-Santos, Tofacitinib and other kinase inhibitors in the treatment of psoriasis, Actas Dermosifiliogr 104 (2013) 304–310.
CR  - [13]	J. Chang, H. Ren, M. Zhao, Y. Chong, W. Zhao, Y. He, et al., Development of a series of novel 4-anilinoquinazoline derivatives possessing quinazoline skeleton: Design, synthesis, EGFR kinase inhibitory efficacy, and evaluation of anticancer activities in vitro, European Journal of Medicinal Chemistry 138 (2017) 669–688.
CR  - [14]	S. Faivre, S. Djelloul, E. Raymond, New paradigms in anticancer therapy: Targeting multiple signaling pathways with kinase inhibitors, Seminars in Oncology 33 (2006) 407–420.
CR  - [15]	R.T. Sataloff, M.M. Johns, K.M. Kost, Quinazolines and anticancer activity: A current perspective, Mujeeb (2017) 1–96.
CR  - [16]	A. Ali, M.E.I. Badawy, R. Shah, W. Rehman, Y. El, Synthesis, characterization and in-silico ADMET screening of mono- and dihydrazides, [Details needed].
CR  - [17]	S.M. Omran, B.M. Abd Razik, M.F. Mahdi, Density functional theory and molecular modeling studies of new 4-(furan-2-yl) thiazol-2-amine derivatives as cyclooxygenase inhibitors, Egyptian Journal of Chemistry 64 (2021) 4833–4841.
CR  - [18]	F.V. Daniel, R.J. Stephen, H.-Y. Chen, B.R. Smith, K.W. Williams, K.D. Kenneth, Molecular properties that influence the oral bioavailability of drug candidates, Journal of Medicinal Chemistry 45 (2002) 2615–2623.
CR  - [19]	M. Ezzat, B. Abd Razik, Molecular modeling design and opioid binding affinity evaluation of new 4-chromanone derivatives, Journal of Microbiology, Biotechnology and Food Sciences [Internet]. 2021 [Details needed].
CR  - [20]	J.L. Dahlin, J. Inglese, M.A. Walters, Mitigating risk in academic preclinical drug discovery, Nature Reviews Drug Discovery 14 (2015) 279–294.
CR  - [21]	W. Sobhi, A. Attoui, T. Lemaoui, A. Erto, Y. Benguerba, In silico drug discovery of acetylcholinesterase and butyrylcholinesterase enzymes inhibitors based on quantitative structure-activity relationship (QSAR) and drug-likeness evaluation, Journal of Molecular Structure 1229 (2021) 129845.
CR  - [22]	A. Daina, O. Michielin, V. Zoete, SwissADME: A free web tool to evaluate pharmacokinetics, druglikeness and medicinal chemistry friendliness of small molecules, Scientific Reports 7 (2017) 42717.
CR  - [23]	M.A. Tantray, I. Khan, H. Hamid, M.S. Alam, A. Dhulap, A. Kalam, Synthesis of benzimidazole-linked-1,3,4-oxadiazole carboxamides as GSK-3 inhibitors with in vivo antidepressant activity, Bioorganic Chemistry 77 (2018) 393–401.
CR  - [24]	S. Ismaeel, M.F. Mahdi, B.M. Abd Razik, Design, synthesis and antibacterial study of new agents having 4-thiazolidinone pharmacophore, Egyptian Journal of Chemistry 63 (2020) 2591–2603.
UR  - https://doi.org/10.33435/tcandtc.1525797
L1  - https://dergipark.org.tr/en/download/article-file/4112429
ER  -