<abstract xmlns="http://www.w3.org/1999/xhtml"><p> Three different series of phosphonate derivatives, b-aminoand fused thiadiazolo/thiadiazine-phosphonates have been synthesized using the addition and/or addition-cyclization protocol of Horner-Wadsworth-Emmons (HWE) reagents to 1,2,4-triazole-3-thiols. The design of potentially antimicrobial and anticancer phosphor esters relied on the results of computer-assisted molecular modeling. All synthesized phosphonates were evaluated for their in vitro antimicrobial activities while anticancer properties were determined for eight out of twenty new phosphonates. The tested phosphonates, except for compounds that have a nitrile moiety, exhibited moderate to significant antimicrobial activity. Nevertheless, the most active compounds were fused thiadiazole-phosphonates, which inhibited the growth of both Gram-negative and Gram-positive bacteria better than b-aminophosphonates and fused thiadiazolophosphonates. In parallel, the antitumor activity screenings of selected phosphonates from each series and substrate 1 were also done. Their antitumor properties against ten carcinoma cell lines, including breast (MCF7, MDA-MB- 231/ ATCC, MDA-MB-435, BT-549), ovarian (IGROVI, OVCAR-3, SK-OV-3), prostate (PX-3, PU-145), and liver (HEPG2), were investigated. The results showed that all synthesized compounds reflected remarkable antitumor activity against breast (especially MDA-MB-231/ATCC and BT-549), and prostate carcinoma cell lines (PC-3 and DU-145), whereas a moderate to good effect on ovarian and liver cancer cells was observed.</p></abstract>

Three different series of phosphonate derivatives, b-aminoand fused thiadiazolo/thiadiazine-phosphonates have been synthesized using the addition and/or addition-cyclization protocol of Horner-Wadsworth-Emmons (HWE) reagents to 1,2,4-triazole-3-thiols. The design of potentially antimicrobial and anticancer phosphor esters relied on the results of computer-assisted molecular modeling. All synthesized phosphonates were evaluated for their in vitro antimicrobial activities while anticancer properties were determined for eight out of twenty new phosphonates. The tested phosphonates, except for compounds that have a nitrile moiety, exhibited moderate to significant antimicrobial activity. Nevertheless, the most active compounds were fused thiadiazole-phosphonates, which inhibited the growth of both Gram-negative and Gram-positive bacteria better than b-aminophosphonates and fused thiadiazolophosphonates. In parallel, the antitumor activity screenings of selected phosphonates from each series and substrate 1 were also done. Their antitumor properties against ten carcinoma cell lines, including breast (MCF7, MDA-MB- 231/ ATCC, MDA-MB-435, BT-549), ovarian (IGROVI, OVCAR-3, SK-OV-3), prostate (PX-3, PU-145), and liver (HEPG2), were investigated. The results showed that all synthesized compounds reflected remarkable antitumor activity against breast (especially MDA-MB-231/ATCC and BT-549), and prostate carcinoma cell lines (PC-3 and DU-145), whereas a moderate to good effect on ovarian and liver cancer cells was observed.

Design, Synthesis and Pharmacological Screening of β-Amino-, Thiadiazole/Thiadiazine-Phosphonate Based Triazole Motifs as Antimicrobial/Cytotoxic Agents

Chemical Industries Division National Research Centre D-12311, Dokki Cairo, Egypt

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Three different series of phosphonate derivatives, b-aminoand fused thiadiazolo/thiadiazine-phosphonates have been synthesized using the addition and/or...

Design, Synthesis and Pharmacological Screening of β-Amino-, Thiadiazole/Thiadiazine-Phosphonate Based Triazole Motifs as Antimicrobial/Cytotoxic Agents

Published Online: Oct 08, 2014

Page range: 267 - 284

Accepted: Apr 30, 2014

DOI: https://doi.org/10.2478/acph-2014-0023

Keywords
β-amino/thiadiazolo/thiadiazino-phosphonates, 1,2,4-triazole-3-thiols, Horner-Wadsworth-Emmons reagents, in vitro antimicrobial/antineoplastic activity

© by Wafaa M. Abdou

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Design, Synthesis and Pharmacological Screening of β-Amino-, Thiadiazole/Thiadiazine-Phosphonate Based Triazole Motifs as Antimicrobial/Cytotoxic Agents

Published Online: Oct 08, 2014

Page range: 267 - 284

Accepted: Apr 30, 2014

DOI: https://doi.org/10.2478/acph-2014-0023

Keywordsβ-amino/thiadiazolo/thiadiazino-phosphonates, 1,2,4-triazole-3-thiols, Horner-Wadsworth-Emmons reagents, in vitro antimicrobial/antineoplastic activity

© by Wafaa M. Abdou

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
β-amino/thiadiazolo/thiadiazino-phosphonates, 1,2,4-triazole-3-thiols, Horner-Wadsworth-Emmons reagents, in vitro antimicrobial/antineoplastic activity