The flavonoid hesperidin methyl chalcone as a potential therapeutic agent for cancer therapy: Molecular docking, in vitro cytotoxicity, and in vivo antitumor activity

Author: Al Hagbani, Turki ; A. Yousif Adam, Fahad ; S. Abu Lila, Amr ; S. Boregowda, Sateesha ; M. D. Rizvi, Syed ; P. Mudagal, Manjunatha ; Hussain, Arshad ; Hussain, Talib ; Khafagy, El-Sayed ; Abdallah, Marwa H.

Hesperidin Me chalcone (HMC) is a methylation product of the flavanone hesperidin, a flavonoid derived from citrus fruits.Many reports have emphasized the analgesic, anti-inflammatory and antioxidant properties of HMC.However, the anticancer potential of HMC has not been fully elucidated.The objective of this study was to assess the possible anticancer potential of HMC.MTT assay was carried out to assess the in vitro cytotoxicity of HMC against using A549 cancer cell line.In addition, the in vivo antitumor activity of HMC was screened against murine Ehrlich ascites carcinoma (EAC) model, in terms of tumor volume, tumor weight, life span, hematol. and biochem. parameters, and compared with that of the anticancer agent, hesperetin.HMC was efficient to suppress the cell viability of A549 cancer cells with an IC₅₀ value of 51.12μM, which was comparable to that of the anticancer agent hesperetin (IC₅₀ = 49.12μM).Similarly, in Ehrlich ascites carcinoma model, HMC significantly inhibited the growth of Ehrlich ascites carcinoma with mutual increase in the life span of HMC-treated mice, compared to EAC control.Most importantly, HMC showed a good safety profile as evidenced by restoring hematol. profile count of RBCs, WBCs, and Hb to the normal levels.HMC also efficiently reduced the oxidative stress in EAC-bearing mice via increasing the levels of GSH, SOD and Catalase.Collectively, HMC exerted a potent anticancer activity and data presented in this work suggest the usefulness of HMC as a promising candidate in cancer therapy.

01 Feb 2023·SAR and QSAR in Environmental Research

QSAR study of tetrahydropteridin derivatives as polo-like kinase 1(PLK1) Inhibitors with molecular docking and dynamics study

Article

Author: Sharma, S. ; Sindhu, J. ; Kumar, P. ; Garima

PLK1 is the key target for dealing with different cancer because it plays an important role in cell proliferation. According to the regulation of OECD, a QSAR model was developed from a dataset of 68 tetrahydropteridin derivatives. Three descriptors (maxHaaCH, ATSC7i, AATS7m) were considered for the development of the QSAR model. The reliability and predictability of the developed QSAR model were evaluated by various statistical parameters (r² = 0.8213, r²_ext = 0.8771 and CCC_ext = 0.9364). The maxHaaCH descriptor is positively correlated to pIC₅₀ whereas, the ATSC7i and AATS7m are negatively correlated with pIC₅₀. The QSAR model explains all the structural features and shows a good correlation with the activity. Based on molecular modelling techniques, five compounds (D1-D5) were designed. Molecular docking and dynamics studies of the most active compound were performed with PDB ID: 2RKU. The results of the present investigation may be employed to identify and develop effective inhibitors for the treatment of PLK1-related pathophysiological disorders.

01 Apr 2013·Bioorganic & Medicinal Chemistry LettersQ4 · MEDICINE

BCR-ABL tyrosine kinase inhibitor pharmacophore model derived from a series of phenylaminopyrimidine-based (PAP) derivatives

Q4 · MEDICINE

Article

Author: Shu Liu ; Li-Hua Zhou ; Rao Fu ; Shen-Xian Qian ; Guang-Wu Li ; Sheng-Ping Chen ; Jing Cui

To reveal novel insights into the inhibition of BCR-ABL tyrosine kinase, pharmacophore mapping studies were performed for a series of phenylaminopyrimidine-based (PAP) derivatives, including imatinib (Gleevec). A seven-point pharmacophore model with one hydrophobic group (H), two hydrogen bond donors (D) and four aromatic rings (R) was developed using phase (pharmacophore alignment & scoring engine). The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with a correlation coefficient of 0.886 and a survival score of 4.97 for training set molecules. The model showed excellent predictive power, with a correlation coefficient of Q(2)=0.768 for an external test set of ten molecules. The results obtained from our studies provide a valuable tool for designing new lead molecules with potent activity.

100 Deals associated with PHA-680626

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Indication	Highest Phase	Country/Location	Organization	Date
Neuroblastoma	Preclinical	Italy	Nerviano Medical Sciences S.r.l	20 Oct 2021
Neuroblastoma	Preclinical	Italy	Sapienza University of Rome	20 Oct 2021
Neuroblastoma	Preclinical	Italy	Nerviano Medical Sciences S.r.l	20 Oct 2021
Neuroblastoma	Preclinical	Italy	Sapienza University of Rome	20 Oct 2021
Philadelphia chromosome positive chronic myelogenous leukemia	Preclinical	Italy	Nerviano Medical Sciences S.r.l	15 Jan 2008
Philadelphia chromosome positive chronic myelogenous leukemia	Preclinical	Italy	Nerviano Medical Sciences S.r.l	15 Jan 2008

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