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<p>Curcumin and its derivatives have gained considerable importance due to their diverse pharmacological properties. This study focuses on DFT calculations, ADME and toxicity profiling, SAR analysis, and biological target prediction of halogenated curcumin derivatives (<b>HCA-HCE</b>). SwissADME was employed to predict pharmacokinetic properties, revealing that all compounds showed satisfactory physiochemical properties, drug-likeness properties, and bioavailability. However, all the compounds either showed moderate solubility or poor solubility. Similarly, the compounds demonstrated favorable lipophilicity values except for <b>HCC</b>. The pharmacokinetic properties results reflect that none of the compounds were a P-gp substrate, and all compounds act as inhibitors of CYP2C9 and CYP3A4. ADMETLab 3.0 was used for toxicological profiling and predicted moderate toxicity for various endpoints. The compounds showed high value in the skin sensitization rule, while for other endpoints, the results varied. Similarly, DFT calculations, performed using the B3LYP/6-311G** basis set, provided insights into the electronic structure, indicating that <b>HCD</b> had the lowest HOMO-LUMO energy gap, suggesting high reactivity, while <b>HCC</b> showed the highest energy gap, reflecting the highest stability among all. Furthermore, <b>HCE</b> demonstrated the highest electrophilicity index, electron-accepting, and electron-donation values, suggesting strong reactivity with biological targets. Similarly, SAR analysis indicated that bromine and chlorine substitutions, particularly at the central chain, enhanced reactivity, electrophilicity, and toxicity. SwissTargetPrediction showed that most of the targets of the compounds are enzymes, lyases, specifically different isoforms of carbonic anhydrase. These findings highlight the therapeutic potential of the compounds and support further experimental, advanced computational, and in vivo/in vitro studies, considering the limitations of basic in silico methods in reflecting complex biological systems.</p>

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Halogenated Curcumin Derivatives: SwissADME/ADMT, DFT and Biological Targets Prediction

  • 期刊论文

  • 发表日期：

    2025年9月12日

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  • Muhammad Mujtaba,
  • Muhammad Imtiaz Shafiq,
  • Adnan Ahmad,
  • Jamelah Saleh Al-Otaibi,
  • Maria Daglia,
  • Haroon Khan

摘要

Curcumin and its derivatives have gained considerable importance due to their diverse pharmacological properties. This study focuses on DFT calculations, ADME and toxicity profiling, SAR analysis, and biological target prediction of halogenated curcumin derivatives (HCA-HCE). SwissADME was employed to predict pharmacokinetic properties, revealing that all compounds showed satisfactory physiochemical properties, drug-likeness properties, and bioavailability. However, all the compounds either showed moderate solubility or poor solubility. Similarly, the compounds demonstrated favorable lipophilicity values except for HCC. The pharmacokinetic properties results reflect that none of the compounds were a P-gp substrate, and all compounds act as inhibitors of CYP2C9 and CYP3A4. ADMETLab 3.0 was used for toxicological profiling and predicted moderate toxicity for various endpoints. The compounds showed high value in the skin sensitization rule, while for other endpoints, the results varied. Similarly, DFT calculations, performed using the B3LYP/6-311G** basis set, provided insights into the electronic structure, indicating that HCD had the lowest HOMO-LUMO energy gap, suggesting high reactivity, while HCC showed the highest energy gap, reflecting the highest stability among all. Furthermore, HCE demonstrated the highest electrophilicity index, electron-accepting, and electron-donation values, suggesting strong reactivity with biological targets. Similarly, SAR analysis indicated that bromine and chlorine substitutions, particularly at the central chain, enhanced reactivity, electrophilicity, and toxicity. SwissTargetPrediction showed that most of the targets of the compounds are enzymes, lyases, specifically different isoforms of carbonic anhydrase. These findings highlight the therapeutic potential of the compounds and support further experimental, advanced computational, and in vivo/in vitro studies, considering the limitations of basic in silico methods in reflecting complex biological systems.