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<p>In material research, a key concept implies that even if a compound is inactive or less active for a certain application, its derivatives may exhibit high activity for the same target. Given the importance of the thermal stability and phase transitions of the new compounds in their separation, purification, and applications at low and high temperatures, the thermal behavior of five new bis(2-alkylsulfenyl-[1,3,4]thiadiazolyl)-5,5′-disulfide derivatives was investigated. In addition, the pharmacokinetic properties and toxicity of new 1,3,4-thiadizole derivatives were predicted due to the importance of 1,3,4-thiadizole scaffolds in the pharmaceutical area and great concern about the toxicity of newly developed compounds as candidates in drug research. Finally, their antibacterial activity was examined in vitro. The impact of molecular mass, carbon chain length, molecular packing, and van der Waals forces on their thermal behavior was studied by TG-DTA and DSC across several heating and cooling cycles. The pharmacokinetics, drug-likeness, medicinal chemistry friendliness, and toxicity of the 1,3,4-thiadiazole-based disulfides were predicted by the SwissADME and TEST tools. The in vitro evaluation of the antibacterial activity of 1,3,4-thiadiazole-based disulfides against <i>Staphylococcus aureus</i> ATCC 25923 (<i>S. Aureus</i>) (gram-positive) and <i>Escherichia coli</i> ATCC 25922 (<i>E. Coli</i>) (gram-negative) was studied via the broth microdilution method in DMSO as a solvent. The 1,3,4-thiadiazole derivatives were non-hygroscopic with no tendency for gas absorption. Their degradations occur through a sharp one-step mass loss, and their decomposition temperatures were not remarkably different (514&#xa0;K for (Bn)<sub>2</sub>TDS and 554&#xa0;K for (C18)<sub>2</sub>TDS). No glass transition was detected. A relationship between molecular mass and a slight increase in melting points for aliphatic substituents was observed (344&#xa0;K for (C8)<sub>2</sub>TDS and 372&#xa0;K for (C18)<sub>2</sub>TDS). The crystallization temperatures were in the range of 283&#xa0;K for (C8)<sub>2</sub>TDS to 324&#xa0;K for (C12)<sub>2</sub>TDS; however, no crystallization was displayed for (Bn)<sub>2</sub>TDS. The substituent effect on the pharmacokinetic properties was demonstrated, and an in vitro study revealed that (Bn)<sub>2</sub>TDS, with a MIC of 62.5&#xa0;µg&#xa0;cm<sup>−3</sup>, exhibited greater potency against <i>S. aureus</i> and <i>E. coli</i> compared to other TDS derivatives probably due to π-stacking interactions of benzyl groups with a certain target. This paper presents the thermal behavior and antibacterial activity of the TDS derivatives for the first time, to the best of our knowledge. The results of this study demonstrated that some TDS derivatives can be promising candidates in the pharmaceutical area, requiring further investigation.</p> Graphical abstract <p></p>

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Substituent impact on thermal behavior and antibacterial activity of bis(2-alkylsulfenyl-[1,3,4]thiadiazolyl)-5,5′-disulfides

  • 期刊论文

  • 发表日期：

    2025年9月5日

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  • Nurul Fatimah Abdul Basir,
  • Syarifah Iliya Nor Za’im,
  • Mahta Ghafarikhaligh,
  • Mohd Rafie Johan,
  • Nader Ghaffari Khaligh

摘要

In material research, a key concept implies that even if a compound is inactive or less active for a certain application, its derivatives may exhibit high activity for the same target. Given the importance of the thermal stability and phase transitions of the new compounds in their separation, purification, and applications at low and high temperatures, the thermal behavior of five new bis(2-alkylsulfenyl-[1,3,4]thiadiazolyl)-5,5′-disulfide derivatives was investigated. In addition, the pharmacokinetic properties and toxicity of new 1,3,4-thiadizole derivatives were predicted due to the importance of 1,3,4-thiadizole scaffolds in the pharmaceutical area and great concern about the toxicity of newly developed compounds as candidates in drug research. Finally, their antibacterial activity was examined in vitro. The impact of molecular mass, carbon chain length, molecular packing, and van der Waals forces on their thermal behavior was studied by TG-DTA and DSC across several heating and cooling cycles. The pharmacokinetics, drug-likeness, medicinal chemistry friendliness, and toxicity of the 1,3,4-thiadiazole-based disulfides were predicted by the SwissADME and TEST tools. The in vitro evaluation of the antibacterial activity of 1,3,4-thiadiazole-based disulfides against Staphylococcus aureus ATCC 25923 (S. Aureus) (gram-positive) and Escherichia coli ATCC 25922 (E. Coli) (gram-negative) was studied via the broth microdilution method in DMSO as a solvent. The 1,3,4-thiadiazole derivatives were non-hygroscopic with no tendency for gas absorption. Their degradations occur through a sharp one-step mass loss, and their decomposition temperatures were not remarkably different (514 K for (Bn)2TDS and 554 K for (C18)2TDS). No glass transition was detected. A relationship between molecular mass and a slight increase in melting points for aliphatic substituents was observed (344 K for (C8)2TDS and 372 K for (C18)2TDS). The crystallization temperatures were in the range of 283 K for (C8)2TDS to 324 K for (C12)2TDS; however, no crystallization was displayed for (Bn)2TDS. The substituent effect on the pharmacokinetic properties was demonstrated, and an in vitro study revealed that (Bn)2TDS, with a MIC of 62.5 µg cm−3, exhibited greater potency against S. aureus and E. coli compared to other TDS derivatives probably due to π-stacking interactions of benzyl groups with a certain target. This paper presents the thermal behavior and antibacterial activity of the TDS derivatives for the first time, to the best of our knowledge. The results of this study demonstrated that some TDS derivatives can be promising candidates in the pharmaceutical area, requiring further investigation.

Graphical abstract