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Synthesis of new chiral 1,3,4-thiadiazole-based di- and tri-arylsulfonamide residues and evaluation of in vitro anti-HIV activity and cytotoxicity

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Abstract

A series of new chiral 1,3,4-thiadiazole-based bis-sulfonamides 4a–4w and tri-sulfonamide analogue 5 was synthesized and evaluated as anti-HIV agents. The reaction of chiral amino acids 1 with sulfonyl chlorides 2, followed by subsequent reaction of resultant N-protected amino acids 2a–2f with thiosemicarbazide in the presence of excess phosphorous oxychloride afforded N-(1-(5-amino-1,3,4-thiadiazol-2-yl)alkyl)-4-arylsulfonamides 3a–3f. Treatment of 2a–2f with substituted sulfonyl chlorides in portions furnished the target bis-sulfonamide analogues 4a–4w in good yields, together with the unexpected 5. The new compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. Compounds 4s were the most active in inhibiting HIV-1 with IC50 = 9.5 μM (SI = 6.6), suggesting to be a new lead in the development of an antiviral agent. Interestingly, compound 5 exhibited significant cytotoxicity of > 4.09 μM and could be a promising antiproliferative agent.

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Acknowledgements

We thank Prof. C. Pannecouque of Rega Institute for Medical Research, Katholieke Universiteit, Leuven, Belgium, for the anti-HIV screening.

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  1. Najim Aboud Al-Masoudi

    Present address: , Constance, Germany

Authors and Affiliations

  1. Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan

    Maria Shafique, Shahid Hameed & Muhammad Moazzam Naseer

  2. Department of Chemistry, College of Science, University of Basrah, Basrah, Iraq

    Najim Aboud Al-Masoudi

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  1. Maria Shafique
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Correspondence to Shahid Hameed or Najim Aboud Al-Masoudi.

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Shafique, M., Hameed, S., Naseer, M.M. et al. Synthesis of new chiral 1,3,4-thiadiazole-based di- and tri-arylsulfonamide residues and evaluation of in vitro anti-HIV activity and cytotoxicity. Mol Divers 22, 957–968 (2018). https://doi.org/10.1007/s11030-018-9851-2

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