Advanced Computational Methodologies Used in the Discovery of New Natural Anticancer Compounds - PubMed (original) (raw)

Review

Advanced Computational Methodologies Used in the Discovery of New Natural Anticancer Compounds

Vivek P Chavda et al. Front Pharmacol. 2021.

Abstract

Natural chemical compounds have been widely investigated for their programmed necrosis causing characteristics. One of the conventional methods for screening such compounds is the use of concentrated plant extracts without isolation of active moieties for understanding pharmacological activity. For the last two decades, modern medicine has relied mainly on the isolation and purification of one or two complicated active and isomeric compounds. The idea of multi-target drugs has advanced rapidly and impressively from an innovative model when first proposed in the early 2000s to one of the popular trends for drug development in 2021. Alternatively, fragment-based drug discovery is also explored in identifying target-based drug discovery for potent natural anticancer agents which is based on well-defined fragments opposite to use of naturally occurring mixtures. This review summarizes the current key advancements in natural anticancer compounds; computer-assisted/fragment-based structural elucidation and a multi-target approach for the exploration of natural compounds.

Keywords: drug antibody conjugate; drug repurposing; fragment-based screening; multi-target approach; natural anticancer compounds; personalized medicine; theranostics.

Copyright © 2021 Chavda, Ertas, Walhekar, Modh, Doshi, Shah, Anand and Chhabria.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1

FIGURE 1

Statistics of globally reported cases and deaths due to various types of cancers in 2020 [Data Collected from (WHO, 2021a)].

FIGURE 2

FIGURE 2

(A) 3D and (B) 2D representation of the best re-docking pose of Trichostatin A (TSA) against HDAC7 (PDB code 3C10) receptor obtained using the Glide-SP algorithm.

FIGURE 3

FIGURE 3

Summary of stepwise structural elucidation techniques of natural products.

FIGURE 4

FIGURE 4

Procedure for fragment-based screening.

FIGURE 5

FIGURE 5

Multitarget based screening of anticancer natural compounds. Pro-inflammatory mediators like TNFα, JL2, JL12, etc. binds to the receptor on the cell surface which undergoes a conformational change and activates JNK 1/2. JNK1/2 phosphorylation leads to apoptosis that releases inflammatory factors like NFKβ that also releases inflammatory factors like TNF-α which plays role in cell death amplification. IL6 activates JAK/STAT pathway that results in cancer cell proliferation. TGFFβ also activates various pathways leading to liver fibrosis. EGFR binds to the cell surface receptor that activates GRB2. Phosphorylation of GRB2 activates the downstream pathway as GABI further activates P13K that activates AKT leading to cell survival. Natural fragments like indole, quinoline, isoquinoline, and piperidine inhibit both the inflammation pathway and EGFR in cancer cell growth.

References

    1. Abdelmohsen U. R., Bayer K., Hentschel U. (2014). Diversity, Abundance and Natural Products of marine Sponge-Associated Actinomycetes. Nat. Prod. Rep. 31, 381–399. 10.1039/c3np70111e - DOI - PubMed
    1. Abdollahpour-Alitappeh M., Lotfinia M., Gharibi T., Mardaneh J., Farhadihosseinabadi B., Larki P., et al. (2019). Antibody-drug Conjugates (ADCs) for Cancer Therapy: Strategies, Challenges, and Successes. J. Cel. Physiol. 234, 5628–5642. 10.1002/jcp.27419 - DOI - PubMed
    1. AlAjmi M. F., Rehman M. T., Hussain A., Rather G. M. (2018). Pharmacoinformatics Approach for the Identification of Polo-like Kinase-1 Inhibitors from Natural Sources as Anti-cancer Agents. Int. J. Biol. Macromolecules 116, 173–181. 10.1016/j.ijbiomac.2018.05.023 - DOI - PubMed
    1. Aljofan M., Riethmacher D. (2019). Anticancer Activity of Metformin: a Systematic Review of the Literature. Future Sci. OA 5, FSO410. 10.2144/fsoa-2019-0053 - DOI - PMC - PubMed
    1. Amaral M. E. A., Nery L. R., Leite C. E., de Azevedo Junior W. F., Campos M. M. (2018). Pre-clinical Effects of Metformin and Aspirin on the Cell Lines of Different Breast Cancer Subtypes. Invest. New Drugs 36, 782–796. 10.1007/s10637-018-0568-y - DOI - PubMed

Publication types

LinkOut - more resources