TY - JOUR
T1 - A convergent multicomponent synthesis, spectral analysis, molecular modelling and docking studies of novel 2H-pyrido[1,2-a]pyrimidine-2,4(3H)-dione derivatives as potential anti-cervical cancer agents
AU - Afza, Nishat
AU - Trivedi, Prince
AU - Bishnoi, Abha
AU - Parveen, Shama
AU - Kumar, Saurabh
AU - Banerjee, Monisha
N1 - Funding Information:
The authors convey their profound thanks to the Head, Department of Chemistry, Lucknow University, for providing laboratory facilities and spectral data analysis. The authors would also like to express their gratitude to the Department of Zoology, University of Lucknow and to the Director, Central Drug Research Institute (CDRI), Lucknow, India for helping in evaluating biological activities and spectroscopic analysis respectively.
Publisher Copyright:
© 2023 Elsevier B.V.
PY - 2023/5/5
Y1 - 2023/5/5
N2 - A series of Novel hybrid 3,3-dimethyl-13-(substituted-phenyl)-3,4,5,13-tetrahydro-1H-pyrido[1′,2′:1,2]pyrimido[4,5-b]quinoline-1,12(2H)-dione derivatives were designed and chemically synthesized in useful yields. The newly synthesized compounds were characterized on the basis of spectral (FT-IR, 1H, 13C NMR, Mass spectral) analyses, and biologically screened in-vitro for their anti-cervical cancer activity against HeLa cancer cell line. The results of cytotoxic evaluation indicated that compounds 7a, 7b, 7c and 7e were appeared to have broad-spectrum cytotoxic activity with IC50 values of 270 μM, 320, 330, and 400 μM, against HeLa cell line. Compound 7a exhibited the most promising inhibitory activity against HeLa cell line as compared to 7b, 7c and 7e. Structural-Activity Relationship (SAR) results show that the presence of electron withdrawing substituents play an important role in the anti-cervical cancer activity of these tested compounds. Moreover, molecular docking studies were conducted to investigate the probable binding conformations of these anti-cancer agents and in-silico ADME (Absorption, Distribution, Metabolism, and Excretion) properties were calculated to predict physicochemical, lipophilicity, pharmacokinetics and medicinal properties of the target compounds.
AB - A series of Novel hybrid 3,3-dimethyl-13-(substituted-phenyl)-3,4,5,13-tetrahydro-1H-pyrido[1′,2′:1,2]pyrimido[4,5-b]quinoline-1,12(2H)-dione derivatives were designed and chemically synthesized in useful yields. The newly synthesized compounds were characterized on the basis of spectral (FT-IR, 1H, 13C NMR, Mass spectral) analyses, and biologically screened in-vitro for their anti-cervical cancer activity against HeLa cancer cell line. The results of cytotoxic evaluation indicated that compounds 7a, 7b, 7c and 7e were appeared to have broad-spectrum cytotoxic activity with IC50 values of 270 μM, 320, 330, and 400 μM, against HeLa cell line. Compound 7a exhibited the most promising inhibitory activity against HeLa cell line as compared to 7b, 7c and 7e. Structural-Activity Relationship (SAR) results show that the presence of electron withdrawing substituents play an important role in the anti-cervical cancer activity of these tested compounds. Moreover, molecular docking studies were conducted to investigate the probable binding conformations of these anti-cancer agents and in-silico ADME (Absorption, Distribution, Metabolism, and Excretion) properties were calculated to predict physicochemical, lipophilicity, pharmacokinetics and medicinal properties of the target compounds.
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U2 - 10.1016/j.molstruc.2023.134982
DO - 10.1016/j.molstruc.2023.134982
M3 - Article
AN - SCOPUS:85147117873
SN - 0022-2860
VL - 1279
JO - Journal of Molecular Structure
JF - Journal of Molecular Structure
M1 - 134982
ER -
