Pyrazoline analogs as potential anticancer agents and their apoptosis, molecular docking, MD simulation, DNA binding and antioxidant studies

Manish Rana; Rizwan Arif; Faez Iqbal Khan; Vikas Maurya; Raja Singh; Md Imam Faizan; Shama Yasmeen; Sajad Hussain Dar; Raquib Alam; Ankita Sahu; Tanveer Ahmad; Rahisuddin

doi:10.1016/j.bioorg.2021.104665

Pyrazoline analogs as potential anticancer agents and their apoptosis, molecular docking, MD simulation, DNA binding and antioxidant studies

Manish Rana, Rizwan Arif, Faez Iqbal Khan, Vikas Maurya, Raja Singh, Md Imam Faizan, Shama Yasmeen, Sajad Hussain Dar, Raquib Alam, Ankita Sahu, Tanveer Ahmad, Rahisuddin^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

36 Citations (Scopus)

Abstract

N-formyl pyrazoline derivatives (3a–3l) were designed and synthesized via Michael addition reaction through cyclization of chalcones with hydrazine hydrate in presence of formic acid. The structural elucidation of N-formyl pyrazoline derivatives was carried out by various spectroscopic techniques such as ¹H, ¹³C NMR, FT-IR, UV–visible spectroscopy, mass spectrometry and elemental analysis. Anticancer activity of the pyrazoline derivatives (3a–3l) was evaluated against human lung cancer (A549), fibrosarcoma cell lines (HT1080) and human primary normal lung cells (HFL-1) by MTT assay. The results of anticancer activity showed that potent analogs 3b and 3d exhibited promising activity against A549 (IC₅₀ = 12.47 ± 1.08 and 14.46 ± 2.76 µM) and HT1080 (IC₅₀ = 11.40 ± 0.66 and 23.74 ± 13.30 µM) but low toxic against the HFL-1 (IC₅₀ = 116.47 ± 43.38 and 152.36 ± 22.18 µM). The anticancer activity of potent derivatives (3b and 3d) against A549 cancer cell line was further confirmed by flow cytometry based approach. DNA binding interactions of the pyrazoline derivatives 3b and 3d have been carried out with calf thymus DNA (Ct-DNA) using absorption, fluorescence and viscosity measurements, circular dichroism and cyclic voltammetry. Antioxidant potential of N-formyl pyrazoline derivatives (3a–3l) has been also estimated through DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical and H₂O_2. Results revealed that all the compounds exhibited significant antioxidant activity. In silico molecular modelling and ADMET properties of pyrazoline derivatives were also studied using PyRx software against topoisomerase II receptor with PDB ID: 1ZXM to explore their best hits. MD simulation of 3b and 3d was also carried out with topoisomerase II for structure–function correlation in a protein. HuTopoII inhibitory activity of the analogs (3a–3l) was examined by relaxation assay at varying concentrations 100–1000 µM.

Original language	English
Article number	104665
Journal	Bioorganic Chemistry
Volume	108
DOIs	https://doi.org/10.1016/j.bioorg.2021.104665
Publication status	Published - Mar 2021
Externally published	Yes

Keywords

Anticancer
Antioxidant
Ct-DNA
MD simulations
Molecular modelling
N-formyl pyrazoline

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bioorg.2021.104665

Cite this

Rana, M., Arif, R., Khan, F. I., Maurya, V., Singh, R., Faizan, M. I., Yasmeen, S., Dar, S. H., Alam, R., Sahu, A., Ahmad, T., & Rahisuddin (2021). Pyrazoline analogs as potential anticancer agents and their apoptosis, molecular docking, MD simulation, DNA binding and antioxidant studies. Bioorganic Chemistry, 108, Article 104665. https://doi.org/10.1016/j.bioorg.2021.104665

@article{9b73073063ed4e47b295189c6a03d6cf,

title = "Pyrazoline analogs as potential anticancer agents and their apoptosis, molecular docking, MD simulation, DNA binding and antioxidant studies",

abstract = "N-formyl pyrazoline derivatives (3a–3l) were designed and synthesized via Michael addition reaction through cyclization of chalcones with hydrazine hydrate in presence of formic acid. The structural elucidation of N-formyl pyrazoline derivatives was carried out by various spectroscopic techniques such as 1H, 13C NMR, FT-IR, UV–visible spectroscopy, mass spectrometry and elemental analysis. Anticancer activity of the pyrazoline derivatives (3a–3l) was evaluated against human lung cancer (A549), fibrosarcoma cell lines (HT1080) and human primary normal lung cells (HFL-1) by MTT assay. The results of anticancer activity showed that potent analogs 3b and 3d exhibited promising activity against A549 (IC50 = 12.47 ± 1.08 and 14.46 ± 2.76 µM) and HT1080 (IC50 = 11.40 ± 0.66 and 23.74 ± 13.30 µM) but low toxic against the HFL-1 (IC50 = 116.47 ± 43.38 and 152.36 ± 22.18 µM). The anticancer activity of potent derivatives (3b and 3d) against A549 cancer cell line was further confirmed by flow cytometry based approach. DNA binding interactions of the pyrazoline derivatives 3b and 3d have been carried out with calf thymus DNA (Ct-DNA) using absorption, fluorescence and viscosity measurements, circular dichroism and cyclic voltammetry. Antioxidant potential of N-formyl pyrazoline derivatives (3a–3l) has been also estimated through DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical and H2O2. Results revealed that all the compounds exhibited significant antioxidant activity. In silico molecular modelling and ADMET properties of pyrazoline derivatives were also studied using PyRx software against topoisomerase II receptor with PDB ID: 1ZXM to explore their best hits. MD simulation of 3b and 3d was also carried out with topoisomerase II for structure–function correlation in a protein. HuTopoII inhibitory activity of the analogs (3a–3l) was examined by relaxation assay at varying concentrations 100–1000 µM.",

keywords = "Anticancer, Antioxidant, Ct-DNA, MD simulations, Molecular modelling, N-formyl pyrazoline",

author = "Manish Rana and Rizwan Arif and Khan, {Faez Iqbal} and Vikas Maurya and Raja Singh and Faizan, {Md Imam} and Shama Yasmeen and Dar, {Sajad Hussain} and Raquib Alam and Ankita Sahu and Tanveer Ahmad and Rahisuddin",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = mar,

doi = "10.1016/j.bioorg.2021.104665",

language = "English",

volume = "108",

journal = "Bioorganic Chemistry",

issn = "0045-2068",

}

TY - JOUR

T1 - Pyrazoline analogs as potential anticancer agents and their apoptosis, molecular docking, MD simulation, DNA binding and antioxidant studies

AU - Rana, Manish

AU - Arif, Rizwan

AU - Khan, Faez Iqbal

AU - Maurya, Vikas

AU - Singh, Raja

AU - Faizan, Md Imam

AU - Yasmeen, Shama

AU - Dar, Sajad Hussain

AU - Alam, Raquib

AU - Sahu, Ankita

AU - Ahmad, Tanveer

AU - Rahisuddin,

PY - 2021/3

Y1 - 2021/3

N2 - N-formyl pyrazoline derivatives (3a–3l) were designed and synthesized via Michael addition reaction through cyclization of chalcones with hydrazine hydrate in presence of formic acid. The structural elucidation of N-formyl pyrazoline derivatives was carried out by various spectroscopic techniques such as 1H, 13C NMR, FT-IR, UV–visible spectroscopy, mass spectrometry and elemental analysis. Anticancer activity of the pyrazoline derivatives (3a–3l) was evaluated against human lung cancer (A549), fibrosarcoma cell lines (HT1080) and human primary normal lung cells (HFL-1) by MTT assay. The results of anticancer activity showed that potent analogs 3b and 3d exhibited promising activity against A549 (IC50 = 12.47 ± 1.08 and 14.46 ± 2.76 µM) and HT1080 (IC50 = 11.40 ± 0.66 and 23.74 ± 13.30 µM) but low toxic against the HFL-1 (IC50 = 116.47 ± 43.38 and 152.36 ± 22.18 µM). The anticancer activity of potent derivatives (3b and 3d) against A549 cancer cell line was further confirmed by flow cytometry based approach. DNA binding interactions of the pyrazoline derivatives 3b and 3d have been carried out with calf thymus DNA (Ct-DNA) using absorption, fluorescence and viscosity measurements, circular dichroism and cyclic voltammetry. Antioxidant potential of N-formyl pyrazoline derivatives (3a–3l) has been also estimated through DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical and H2O2. Results revealed that all the compounds exhibited significant antioxidant activity. In silico molecular modelling and ADMET properties of pyrazoline derivatives were also studied using PyRx software against topoisomerase II receptor with PDB ID: 1ZXM to explore their best hits. MD simulation of 3b and 3d was also carried out with topoisomerase II for structure–function correlation in a protein. HuTopoII inhibitory activity of the analogs (3a–3l) was examined by relaxation assay at varying concentrations 100–1000 µM.

AB - N-formyl pyrazoline derivatives (3a–3l) were designed and synthesized via Michael addition reaction through cyclization of chalcones with hydrazine hydrate in presence of formic acid. The structural elucidation of N-formyl pyrazoline derivatives was carried out by various spectroscopic techniques such as 1H, 13C NMR, FT-IR, UV–visible spectroscopy, mass spectrometry and elemental analysis. Anticancer activity of the pyrazoline derivatives (3a–3l) was evaluated against human lung cancer (A549), fibrosarcoma cell lines (HT1080) and human primary normal lung cells (HFL-1) by MTT assay. The results of anticancer activity showed that potent analogs 3b and 3d exhibited promising activity against A549 (IC50 = 12.47 ± 1.08 and 14.46 ± 2.76 µM) and HT1080 (IC50 = 11.40 ± 0.66 and 23.74 ± 13.30 µM) but low toxic against the HFL-1 (IC50 = 116.47 ± 43.38 and 152.36 ± 22.18 µM). The anticancer activity of potent derivatives (3b and 3d) against A549 cancer cell line was further confirmed by flow cytometry based approach. DNA binding interactions of the pyrazoline derivatives 3b and 3d have been carried out with calf thymus DNA (Ct-DNA) using absorption, fluorescence and viscosity measurements, circular dichroism and cyclic voltammetry. Antioxidant potential of N-formyl pyrazoline derivatives (3a–3l) has been also estimated through DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical and H2O2. Results revealed that all the compounds exhibited significant antioxidant activity. In silico molecular modelling and ADMET properties of pyrazoline derivatives were also studied using PyRx software against topoisomerase II receptor with PDB ID: 1ZXM to explore their best hits. MD simulation of 3b and 3d was also carried out with topoisomerase II for structure–function correlation in a protein. HuTopoII inhibitory activity of the analogs (3a–3l) was examined by relaxation assay at varying concentrations 100–1000 µM.

KW - Anticancer

KW - Antioxidant

KW - Ct-DNA

KW - MD simulations

KW - Molecular modelling

KW - N-formyl pyrazoline

UR - http://www.scopus.com/inward/record.url?scp=85100505443&partnerID=8YFLogxK

U2 - 10.1016/j.bioorg.2021.104665

DO - 10.1016/j.bioorg.2021.104665

M3 - Article

C2 - 33571809

AN - SCOPUS:85100505443

SN - 0045-2068

VL - 108

JO - Bioorganic Chemistry

JF - Bioorganic Chemistry

M1 - 104665

ER -

Pyrazoline analogs as potential anticancer agents and their apoptosis, molecular docking, MD simulation, DNA binding and antioxidant studies

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this