Exploring the anticancer properties of indole pyrimidine derivatives: Synthesis, structural insights, docking analysis, and in vitro evaluation

HM Pallavi; VH Kameshwar; Fares Hezam Al-Ostoot; Shaukath Ara Khanum

Chemical Physics Impact (Dec 2024)

Exploring the anticancer properties of indole pyrimidine derivatives: Synthesis, structural insights, docking analysis, and in vitro evaluation

HM Pallavi,
VH Kameshwar,
Fares Hezam Al-Ostoot,
Shaukath Ara Khanum

Affiliations

HM Pallavi: Department of Chemistry, Yuvaraja's College, University of Mysore, Mysuru, India
VH Kameshwar: Department of Biochemistry, Adichunchanagiri Institute of Medical Sciences, Adichunchanagiri University, B.G. Nagara, Mandya, India; Adichunchanagiri School of Natural Sciences, Adichunchanagiri University-Centre for Research and Innovation, Adichunchanagiri University, B.G. Nagara, Mandya, India
Fares Hezam Al-Ostoot: Department of Chemistry, Yuvaraja's College, University of Mysore, Mysuru, India; Department of Biochemistry, Faculty of Education & Science, Albaydha University, Albaydha, Yemen; Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy; Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University, Amsterdam, the Netherlands; Corresponding author at: Department of Biochemistry, Albaydha University, Albaydha, Yemen.
Shaukath Ara Khanum: Department of Chemistry, Yuvaraja's College, University of Mysore, Mysuru, India; Corresponding author at: Department of Chemistry, Yuvaraja's College, University of Mysore, Mysuru, India.

Journal volume & issue: Vol. 9
p. 100730

Abstract

Read online

The nitrogen containing heterocyclic and chalcones moiety widely recognized as favorable combination of diagnostic and therapeutic facilities in medicinal chemistry. In particular, indole analogs play a very important medicinal role in pharmacology activities, hence, drugs like pindolol, indomethacin, oxypertine, ellipticine, arbidol and ate viridine are well known in market. In this view, the title compounds 4(a-j) were synthesized in good yield. The purified compounds were explained by spectroscopic procedures (FT-IR, 1H NMR, 13CNMR, and LC-MS), and lastly, all synthetic compounds have in-vitro efficacy assessed against the HeLa human cervical cancer and MCF-7 human breast cancer cell lines, and their efficacy was compared to that of the well-known anticancer drug methotrexate (Methotrexate). Compounds 4a, 4b, 4c, and 4e from the series (4a-j) demonstrated the most notable inhibitory activity. The cytotoxicity evaluation of these newly synthesized compounds revealed that 4a, 4b, 4c, and 4e were the most toxic to HeLa cells, with IC50 values for growth inhibition of 20.41 ± 3.14, 23.54 ± 3.27, 24.77 ± 2.14, and 26.10 ± 1.58, respectively. These compounds exhibited an even stronger growth-inhibitory effect on MCF-7 cells, with IC50 values of 18.84 ± 2.69, 19.45 ± 3.14, 22.83 ± 2.68, and 21.80 ± 1.68, respectively. In comparison, methotrexate (Methotrexate) showed IC50 values of 28.29 ± 1.0 for HeLa cells and 45.08 ± 2.61 for MCF-7 cells. Additionally, compounds 4a, 4b, 4c, and 4e played a crucial role in interacting with the catalytic domain of PDE3, demonstrating IC50 values for PDE3A inhibition of 8.05 ± 1.27, 7.55 ± 2.14, 15.09 ± 1.54, and 17.12 ± 3.14, respectively. These results are compared with Cilostazol, a known PDE inhibitor, which exhibited an IC50 of 0.00368 ± 3.14. In-silico studies revealed that compounds (4a, 4b, and 4c) are comparatively very efficient in binding with PDE3A which was further validated with MMGBSA and MDSs.

Published in Chemical Physics Impact

ISSN: 2667-0224 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Physics; Science: Chemistry
Website: https://www.journals.elsevier.com/chemical-physics-impact/

About the journal

Abstract

Keywords