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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Structure-Activity Relationship Insight of Naturally Occurring Bioactive Molecules and Their Derivatives Against Non-Small Cell Lung Cancer: A Comprehensive Review

Author(s): Subham Das, Shubham Roy, Seikh Batin Rahaman, Saleem Akbar, Bahar Ahmed*, Debojyoti Halder, Anu Kunnath Ramachandran and Alex Joseph*

Volume 29, Issue 39, 2022

Published on: 15 August, 2022

Page: [6030 - 6062] Pages: 33

DOI: 10.2174/0929867329666220509112423

Price: $65


Background: Non-small cell lung cancer (NSCLC) is a deadly disease that affects millions globally and its treatment includes surgery, chemotherapy, and radiotherapy. Chemotherapy and radiotherapy have many disadvantages, which include potential harmful side effects. Due to the widespread use of drugs in lung cancer, drug treatment becomes challenging due to multidrug resistance and adverse reactions. According to the recent findings, natural products (NPs) and their derivatives are being used to inhibit and suppress cancer cells.

Objective: Our objective is to highlight the importance of phytochemicals for treating NSCLC by focusing on the structural features essential for the desired activity with fewer side effects compared to synthetic molecules.

Methods: This review incorporated data from the most recent literature, including in vitro, in vivo, nanoformulation-based recent advancements, and clinical trials, as well as the structure-activity relationship (SAR), described for a variety of possible natural bioactive molecules in the treatment of NSCLC.

Results: The analysis of data from recent in vitro, in vivo studies and ongoing clinical trials are highlighted. The SAR studies of potential NPs signify the presence of several common structural features that can be used to guide future drug design and development.

Conclusion: The role of NPs in the battle against NSCLC can be effective, as evidenced by their structural diversity and affinity toward various molecular targets. The main purpose of the review is to gather information about NPs used in the treatment of NSCLC.

Keywords: Lung cancer, natural products, treatments, chemotherapy, SAR, machine learning, medicinal chemistry.

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RCSB PDB. 7A2A: Crystal structure of EGFR-T790M/V948R in complex with spebrutinib and EAI001. Available from: (accessed Jun 17, 2021).
7JU5: Structure of RET protein tyrosine kinase in complex with pralsetinib. Available from: (accessed Jun 17, 2021).
RCSB PDB. 6SM8: Human jak1 kinase domain in complex with inhibitor Available from:
RCSB PDB. 6SLG: Human ERK2 with ERK1/2 inhibitor, AZD0364. Available from:
RCSB PDB. 6MX8: Crystal structure of anaplastic lymphoma kinase (ALK) bound by Brigatinib. Available from: (accessed Jun 17, 2021).
RCSB PDB. 5YE4: Crystal structure of the complex of di-acetylated histone H4 and 1A9D7 Fab fragment. Available from:
5YE3: Crystal structure of the complex of di-acetylated histone H4 and 2A7D9 Fab fragment Available from: (accessed Jun 17, 2021).
RCSB PDB. 5YU9: Crystal structure of EGFR 696-1022 T790M in complex with Ibrutinib. Available from: (accessed Jun 17, 2021).
RCSB PDB. 5GNK: Crystal structure of EGFR 696-988 T790M in complex with LXX-6-34 Available from: (accessed Jun 17, 2021).
RCSB PDB. 5UGA: Crystal structure of the EGFR kinase domain (L858R, T790M, V948R) in complex with 4-(4-{[2-{[(3S)-1-acetylpyrrolidin-3-yl]amino}-9-(propan- 2-yl)-9H-purin-6-yl]amino}phenyl)-1-methylpiperazin-1-ium. Available from:
RCSB PDB. 5UGC: Crystal structure of the EGFR kinase domain (L858R, T790M, V948R) in complex with a covalent inhibitor N-[(3R,4R)-4-fluoro-1-{6-[(3- methoxy-1-methyl-1H-pyrazol-4-yl)amino]-9-methyl-9H-purin-2-yl} pyrrolidin-3-yl]propanamide. Available from: (accessed Jun 17, 2021).
RCSB PDB. 5UG8: Crystal structure of the EGFR kinase domain (L858R, T790M, V948R) in complex with a covalent inhibitor N-[(3R,4R)-4-fluoro-1-{6-[(1-methyl- 1H-pyrazol-4-yl)amino]-9-(propan-2-yl)-9H-purin-2-yl}pyrrolidin-3-yl]propanamide. Available from: (accessed Jun 17, 2021).
RCSB PDB. 5UG9: Crystal structure of the EGFR kinase domain (L858R, T790M, V948R) in complex with a covalent inhibitor N-[(3R,4R)-4-fluoro-1-{6-[(3- methoxy-1-methyl-1H-pyrazol-4-yl)amino]-9-(propan-2-yl)-9H-purin-2-yl}pyrrolidin-3-yl]propanamide. Available from:
RCSB PDB. 5HLW: Crystal structure of c-Met mutant Y1230H in complex with compound 14. Available from: (accessed Jun 17, 2021).
RCSB PDB. 5HO6: Crystal structure of CMET in complex with cmpd. Available from: (accessed Jun 17, 2021).
RCSB PDB. 5HNI: CRYSTAL STRUCTURE OF CMET WT with compound 3 Available from:
RCSB PDB. 5FTQ: Crystal structure of the ALK kinase domain in complex with Cmpd 17 Available from: (accessed Jun 17, 2021).
RCSB PDB. 5HG5: EGFR (L858R, T790M, V948R) in complex with N-{3-[(2-{[4-(4-methylpiperazin-1-yl) phenyl]amino}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy] phenyl}prop-2-enamide Available from: (accessed Jun 17, 2021).
RCSB PDB. 5HG8: EGFR (L858R, T790M, V948R) in complex with N-[3-({2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)phenyl]prop-2-enamide Available from:
RCSB PDB. 5HG7: EGFR (L858R, T790M, V948R) in complex with 1-{(3R,4R)-3-[5-Chloro-2-(1-methyl-1H-pyrazol-4-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxymethyl]-4-methoxy-pyrrolidin-1-yl}propenone (PF-06459988) Available from:
RCSB PDB. 4RQR: Crystal Structure of Human Glutaredoxin with MESNA Available from: (accessed Jun 17, 2021).

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