Identification of Potential Descriptors of Water-soluble Fullerene Derivatives Responsible for Antitumor Effects on Lung Cancer Cells Via QSAR Analysis

Overview

Journal Comput Struct Biotechnol J

Specialty Biotechnology

Date 2021 Feb 18

PMID 33598097

Citations 7

Authors

Hung-Jin Huang

Margarita Chetyrkina

Chui-Wei Wong

Olga A Kraevaya

Alexander V Zhilenkov

Ilya I Voronov

Pei-Hwa Wang

Pavel A Troshin

Shan-Hui Hsu

Affiliations

Soon will be listed here.

Abstract

Water-soluble fullerene derivatives are actively investigated as potential drugs for cancer treatment due to their favorable membranotropic properties. Herein, cytotoxic effects of twenty fullerene derivatives with different solubilizing addends were evaluated in three different types of non-small-cell lung carcinoma (NSCLC). The potential structural descriptors of the solubilizing addends related to the inhibitory activities on each type of lung cancer cell were investigated by the quantitative structure-activity relationship (QSAR) approach. The determination coefficient for the recommended QSAR model were 0.9325, 0.8404, and 0.9011 for A549, H460, and H1299 cell lines, respectively. The results revealed that the chemical features of the fullerene-based compounds including aromatic bonds, sulfur-containing aromatic rings, and oxygen atoms are favored properties and promote the inhibitory effects on H460 and H1299 cells. Particularly, thiophene moiety is the key functional group, which was positively correlated with strong inhibitory effects on the three types of lung cancer cells. The useful information obtained from our regression models may lead to the design of more efficient inhibitors of the three types of NSCLC.

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References

Prylutska S, Politenkova S, Afanasieva K, Korolovych V, Bogutska K, Sivolob A . A nanocomplex of C fullerene with cisplatin: design, characterization and toxicity. Beilstein J Nanotechnol. 2017; 8:1494-1501. PMC: 5530603. DOI: 10.3762/bjnano.8.149. View

Liu D, Ertay A, Hill C, Zhou Y, Li J, Zou Y . ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer. Cell Death Dis. 2020; 11(4):224. PMC: 7142079. DOI: 10.1038/s41419-020-2415-2. View

Zhang P, Tao H, Yu L, Zhou L, Zhu C . Developing protein arginine methyltransferase 1 (PRMT1) inhibitor TC-E-5003 as an antitumor drug using INEI drug delivery systems. Drug Deliv. 2020; 27(1):491-501. PMC: 7170320. DOI: 10.1080/10717544.2020.1745327. View

Hsieh F, Zhilenkov A, Voronov I, Khakina E, Mischenko D, Troshin P . Water-Soluble Fullerene Derivatives as Brain Medicine: Surface Chemistry Determines If They Are Neuroprotective and Antitumor. ACS Appl Mater Interfaces. 2017; 9(13):11482-11492. DOI: 10.1021/acsami.7b01077. View

Dong J, Li B, Lin D, Zhou Q, Huang D . Advances in Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer Based on Accurate Molecular Typing. Front Pharmacol. 2019; 10:230. PMC: 6424010. DOI: 10.3389/fphar.2019.00230. View

Dako F, Hota P, Kahn M, Kumaran M, Agosto O . Post-lung transplantation abdominopelvic complications: the role of multimodal imaging. Abdom Radiol (NY). 2019; 45(4):1202-1213. DOI: 10.1007/s00261-019-02229-3. View

Kraevaya O, Peregudov A, Fedorova N, Klimova R, Godovikov I, Mishchenko D . Thiophene-based water-soluble fullerene derivatives as highly potent antiherpetic pharmaceuticals. Org Biomol Chem. 2020; 18(42):8702-8708. DOI: 10.1039/d0ob01826k. View

Andriani F, Bertolini G, Facchinetti F, Baldoli E, Moro M, Casalini P . Conversion to stem-cell state in response to microenvironmental cues is regulated by balance between epithelial and mesenchymal features in lung cancer cells. Mol Oncol. 2015; 10(2):253-71. PMC: 5528953. DOI: 10.1016/j.molonc.2015.10.002. View

Vereshchaka I, Bulgakova N, Maznychenko A, Gonchar O, Prylutskyy Y, Ritter U . C Fullerenes Diminish Muscle Fatigue in Rats Comparable to -acetylcysteine or β-Alanine. Front Physiol. 2018; 9:517. PMC: 5962757. DOI: 10.3389/fphys.2018.00517. View

10.

Schliekelman M, Taguchi A, Zhu J, Dai X, Rodriguez J, Celiktas M . Molecular portraits of epithelial, mesenchymal, and hybrid States in lung adenocarcinoma and their relevance to survival. Cancer Res. 2015; 75(9):1789-800. PMC: 4846295. DOI: 10.1158/0008-5472.CAN-14-2535. View

11.

Schulz M, Salamero-Boix A, Niesel K, Alekseeva T, Sevenich L . Microenvironmental Regulation of Tumor Progression and Therapeutic Response in Brain Metastasis. Front Immunol. 2019; 10:1713. PMC: 6667643. DOI: 10.3389/fimmu.2019.01713. View

12.

Zheng T, Wan X, Zhang Q, Jin B, Peng R . Catechol amide derivatized polyhydroxylated fullerene as potential chelating agents of radionuclides: Synthesis, reactive oxygen species scavenging, and cytotoxic studies. J Inorg Biochem. 2019; 203:110921. DOI: 10.1016/j.jinorgbio.2019.110921. View

13.

Gramec D, Peterlin Masic L, Dolenc M . Bioactivation potential of thiophene-containing drugs. Chem Res Toxicol. 2014; 27(8):1344-58. DOI: 10.1021/tx500134g. View

14.

Mukherjee A, Paul M, Mukherjee S . Recent Progress in the Theranostics Application of Nanomedicine in Lung Cancer. Cancers (Basel). 2019; 11(5). PMC: 6562381. DOI: 10.3390/cancers11050597. View

15.

Dzhemilev U, Khuzin A, Akhmetov A, Dyakonov V, Dzhemileva L, Yunusbaeva M . Synthesis of C Fullerene-Quadricyclane Hybrid Compound and Its Preliminary In Vitro Antitumor Activity in Combination with Cisplatin. ACS Omega. 2019; 4(14):15929-15934. PMC: 6776965. DOI: 10.1021/acsomega.9b01982. View

16.

Grebinyk A, Prylutska S, Buchelnikov A, Tverdokhleb N, Grebinyk S, Evstigneev M . C Fullerene as an Effective Nanoplatform of Alkaloid Berberine Delivery into Leukemic Cells. Pharmaceutics. 2019; 11(11). PMC: 6920783. DOI: 10.3390/pharmaceutics11110586. View

17.

Sergeeva V, Kraevaya O, Ershova E, Kameneva L, Malinovskaya E, Dolgikh O . Antioxidant Properties of Fullerene Derivatives Depend on Their Chemical Structure: A Study of Two Fullerene Derivatives on HELFs. Oxid Med Cell Longev. 2019; 2019:4398695. PMC: 6360044. DOI: 10.1155/2019/4398695. View

18.

Arbour K, Riely G . Systemic Therapy for Locally Advanced and Metastatic Non-Small Cell Lung Cancer: A Review. JAMA. 2019; 322(8):764-774. DOI: 10.1001/jama.2019.11058. View

19.

Cheng M, Jolly S, Quarshie W, Kapadia N, Vigneau F, Kong F . Modern Radiation Further Improves Survival in Non-Small Cell Lung Cancer: An Analysis of 288,670 Patients. J Cancer. 2019; 10(1):168-177. PMC: 6329848. DOI: 10.7150/jca.26600. View

20.

Karacosta L, Anchang B, Ignatiadis N, Kimmey S, Benson J, Shrager J . Mapping lung cancer epithelial-mesenchymal transition states and trajectories with single-cell resolution. Nat Commun. 2019; 10(1):5587. PMC: 6898514. DOI: 10.1038/s41467-019-13441-6. View