TY - JOUR
T1 - Pregnenolone derivatives as potential anti-lung cancer agents
T2 - A combined in silico and in vitro approach
AU - Sethi, Arun
AU - Yadav, Priyanka
AU - Singh, Ranvijay Pratap
AU - Kumar, Saurabh
AU - Parveen, Shama
AU - Singh, Asmita
AU - Yadav, Astha
AU - Banerjee, Monisha
N1 - Funding Information:
SP is grateful to CSIR (09/107(0399)/2018‐EMR‐1) for research fellowships. The authors also acknowledge the Centre of Excellence scheme, Government of Uttar Pradesh, India for cell culture facility at Department of Zoology, University of Lucknow, Lucknow. The authors are thankful to the Central facility for spectral data H NMR, C NMR, and 2D NMR provided by Department of Chemistry and ESI‐MS from SAIF division of Central Drugs Research Institute of Lucknow (CDRI), Lucknow. 1 13
Funding Information:
SP is grateful to CSIR (09/107(0399)/2018-EMR-1) for research fellowships. The authors also acknowledge the Centre of Excellence scheme, Government of Uttar Pradesh, India for cell culture facility at Department of Zoology, University of Lucknow, Lucknow. The authors are thankful to the Central facility for spectral data 1H NMR, 13C NMR, and 2D NMR provided by Department of Chemistry and ESI-MS from SAIF division of Central Drugs Research Institute of Lucknow (CDRI), Lucknow.
Publisher Copyright:
© 2022 The Chemical Society Located in Taipei & Wiley-VCH GmbH.
PY - 2022/6
Y1 - 2022/6
N2 - Synthesis of C-3 and C-20 pregnenolone derivatives using Steglich and Heck reaction has been reported. The structures of compounds were established by 1H, 13C NMR, NOESY, FT-IR, and ESI-MS. The anticancer activity against lung cancer proficiency assessment was performed using the prediction of activity spectra for substances (PASS) technique and the results were compared with the FDA-approved lung cancer drug dacomitinib. Molecular docking studies were carried out to investigate the inhibitory action of steroidal derivatives against the lung cancer cell protein (2ITO). The result of the docking exhibited a significant inhibitory action against the lung cancer protein (2ITO) and the binding energy (ΔG) values of 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 against the protein 2ITO were found to be −10.1, −10.8, −9.2, −9.4, −10.1, −9.4, −11.0, −10.9, −9.7, and −9.5 Kcal/mol, respectively. In vitro lung cancer activity analyses of these compounds against lung cancer cell line (A549) showed that compounds 2 and 3 were more potent than other compounds. Results of in silico and in vitro analysis revealed that they showed good correlation. Drugs likeness and ADMET analysis of all derivatives have also been studied.
AB - Synthesis of C-3 and C-20 pregnenolone derivatives using Steglich and Heck reaction has been reported. The structures of compounds were established by 1H, 13C NMR, NOESY, FT-IR, and ESI-MS. The anticancer activity against lung cancer proficiency assessment was performed using the prediction of activity spectra for substances (PASS) technique and the results were compared with the FDA-approved lung cancer drug dacomitinib. Molecular docking studies were carried out to investigate the inhibitory action of steroidal derivatives against the lung cancer cell protein (2ITO). The result of the docking exhibited a significant inhibitory action against the lung cancer protein (2ITO) and the binding energy (ΔG) values of 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 against the protein 2ITO were found to be −10.1, −10.8, −9.2, −9.4, −10.1, −9.4, −11.0, −10.9, −9.7, and −9.5 Kcal/mol, respectively. In vitro lung cancer activity analyses of these compounds against lung cancer cell line (A549) showed that compounds 2 and 3 were more potent than other compounds. Results of in silico and in vitro analysis revealed that they showed good correlation. Drugs likeness and ADMET analysis of all derivatives have also been studied.
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U2 - 10.1002/jccs.202200040
DO - 10.1002/jccs.202200040
M3 - Article
AN - SCOPUS:85129393900
SN - 0009-4536
VL - 69
SP - 872
EP - 883
JO - Journal of the Chinese Chemical Society
JF - Journal of the Chinese Chemical Society
IS - 6
ER -
