Synthesis, biological evaluation, molecular docking, molecular dynamics simulation, and ADME studies of novel carbazole-aniline hybrids as cytotoxic agents.

BMC chemistry · 2026 · Benefit · Low evidence

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BenefitLow evidencePaper 6638

Study snapshot

PublicationBMC chemistry · 2026

Study typein_vitro

Reported directionBenefit

Evidence ratingLow

Abstract

A novel series of seven carbazole-aniline hybrids (5a-5 g) were designed, synthesized, and evaluated as potential anticancer agents. Among them, compound 5e, bearing a para-methoxy substituent, emerged as the most potent candidate, demonstrating significant cytotoxicity against breast cancer (MCF-7) and colon cancer (SW480) cell lines with IC₅₀ values of 26.4 ± 2.54 µM and 34.5 ± 1.69 µM, respectively. Notably, its activity against MCF-7 was comparable to the reference drug Erlotinib (IC₅₀ = 39.3 µM). Structure-activity relationship studies revealed that electron-donating groups significantly enhance cytotoxic effects, while electron-withdrawing substitutions diminish activity. Molecular docking studies showed that compound 5e binds effectively to the EGFR active site with a binding energy of -8.6 kcal/mol, forming key hydrogen bonds with critical residues Asp831 and Thr766. Molecular dynamics simulations further confirmed the stability of the 5e-EGFR complex. In silico ADME predictions indicated favorable drug-like properties for all compounds, consistent with Lipinski's Rule of Five. Based on its potent cytotoxicity, strong target binding, and optimal pharmacokinetic profile, compound 5e is identified as a promising lead candidate for further development as an EGFR-targeting anticancer agent.

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AI evidence extraction

Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.

Study typein_vitro

Effect directionbenefit

PopulationNot supplied

Sample sizeNot supplied

ExposureNot supplied

Evidence strengthLowConfidence: 74% · Peer reviewed: yes

Main findings

Seven carbazole-aniline hybrids (5a–5g) were synthesized and evaluated for cytotoxicity; compound 5e showed the strongest activity with IC50 26.4 ± 2.54 µM (MCF-7) and 34.5 ± 1.69 µM (SW480), with MCF-7 activity comparable to erlotinib (IC50 39.3 µM). Docking indicated 5e binds the EGFR active site (binding energy −8.6 kcal/mol) with hydrogen bonds to Asp831 and Thr766, and molecular dynamics suggested a stable 5e–EGFR complex; ADME predictions were favorable for all compounds and consistent with Lipinski’s Rule of Five.

Outcomes measured

Cytotoxicity (IC50) in MCF-7 breast cancer cell line
Cytotoxicity (IC50) in SW480 colon cancer cell line
EGFR binding energy (molecular docking)
Stability of 5e–EGFR complex (molecular dynamics simulation)
In silico ADME / drug-likeness (Lipinski Rule of Five)

View raw extracted JSON

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  "outcomes": [
    "Cytotoxicity (IC50) in MCF-7 breast cancer cell line",
    "Cytotoxicity (IC50) in SW480 colon cancer cell line",
    "EGFR binding energy (molecular docking)",
    "Stability of 5e–EGFR complex (molecular dynamics simulation)",
    "In silico ADME / drug-likeness (Lipinski Rule of Five)"
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  "main_findings": "Seven carbazole-aniline hybrids (5a–5g) were synthesized and evaluated for cytotoxicity; compound 5e showed the strongest activity with IC50 26.4 ± 2.54 µM (MCF-7) and 34.5 ± 1.69 µM (SW480), with MCF-7 activity comparable to erlotinib (IC50 39.3 µM). Docking indicated 5e binds the EGFR active site (binding energy −8.6 kcal/mol) with hydrogen bonds to Asp831 and Thr766, and molecular dynamics suggested a stable 5e–EGFR complex; ADME predictions were favorable for all compounds and consistent with Lipinski’s Rule of Five.",
  "effect_direction": "benefit",
  "limitations": [],
  "evidence_strength": "low",
  "confidence": 0.74,
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  "keywords": [
    "carbazole-aniline hybrids",
    "cytotoxicity",
    "MCF-7",
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    "Lipinski"
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AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.

Identifiers and source

DOI: 10.1186/s13065-026-01744-x
PubMed: 41691293

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