Design, Synthesis and Pharmacological Screening of β-Amino-, Thiadiazole/Thiadiazine-Phosphonate Based Triazole Motifs as Antimicrobial/Cytotoxic Agents
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 ant...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Sciendo
2014-09-01
|
| Series: | Acta Pharmaceutica |
| Subjects: | |
| Online Access: | https://doi.org/10.2478/acph-2014-0023 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832574197867479040 |
|---|---|
| author | Abdou Wafaa M. Ganoub Neven A. Sabry Eman |
| author_facet | Abdou Wafaa M. Ganoub Neven A. Sabry Eman |
| author_sort | Abdou Wafaa M. |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-efbc86feea1141be92813988b95b4c86 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2014-09-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-efbc86feea1141be92813988b95b4c862025-02-02T00:32:27ZengSciendoActa Pharmaceutica1846-95582014-09-0164326728410.2478/acph-2014-0023acph-2014-0023Design, Synthesis and Pharmacological Screening of β-Amino-, Thiadiazole/Thiadiazine-Phosphonate Based Triazole Motifs as Antimicrobial/Cytotoxic AgentsAbdou Wafaa M.0Ganoub Neven A.1Sabry Eman2Chemical Industries Division National Research Centre D-12311, Dokki Cairo, EgyptChemical Industries Division National Research Centre D-12311, Dokki Cairo, EgyptChemical Industries Division National Research Centre D-12311, Dokki Cairo, EgyptThree 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.https://doi.org/10.2478/acph-2014-0023β-amino/thiadiazolo/thiadiazino-phosphonates1,2,4-triazole-3-thiolshorner-wadsworth-emmons reagentsin vitro antimicrobial/antineoplastic activity |
| spellingShingle | Abdou Wafaa M. Ganoub Neven A. Sabry Eman Design, Synthesis and Pharmacological Screening of β-Amino-, Thiadiazole/Thiadiazine-Phosphonate Based Triazole Motifs as Antimicrobial/Cytotoxic Agents Acta Pharmaceutica β-amino/thiadiazolo/thiadiazino-phosphonates 1,2,4-triazole-3-thiols horner-wadsworth-emmons reagents in vitro antimicrobial/antineoplastic activity |
| title | Design, Synthesis and Pharmacological Screening of β-Amino-, Thiadiazole/Thiadiazine-Phosphonate Based Triazole Motifs as Antimicrobial/Cytotoxic Agents |
| title_full | Design, Synthesis and Pharmacological Screening of β-Amino-, Thiadiazole/Thiadiazine-Phosphonate Based Triazole Motifs as Antimicrobial/Cytotoxic Agents |
| title_fullStr | Design, Synthesis and Pharmacological Screening of β-Amino-, Thiadiazole/Thiadiazine-Phosphonate Based Triazole Motifs as Antimicrobial/Cytotoxic Agents |
| title_full_unstemmed | Design, Synthesis and Pharmacological Screening of β-Amino-, Thiadiazole/Thiadiazine-Phosphonate Based Triazole Motifs as Antimicrobial/Cytotoxic Agents |
| title_short | Design, Synthesis and Pharmacological Screening of β-Amino-, Thiadiazole/Thiadiazine-Phosphonate Based Triazole Motifs as Antimicrobial/Cytotoxic Agents |
| title_sort | design synthesis and pharmacological screening of β amino thiadiazole thiadiazine phosphonate based triazole motifs as antimicrobial cytotoxic agents |
| topic | β-amino/thiadiazolo/thiadiazino-phosphonates 1,2,4-triazole-3-thiols horner-wadsworth-emmons reagents in vitro antimicrobial/antineoplastic activity |
| url | https://doi.org/10.2478/acph-2014-0023 |
| work_keys_str_mv | AT abdouwafaam designsynthesisandpharmacologicalscreeningofbaminothiadiazolethiadiazinephosphonatebasedtriazolemotifsasantimicrobialcytotoxicagents AT ganoubnevena designsynthesisandpharmacologicalscreeningofbaminothiadiazolethiadiazinephosphonatebasedtriazolemotifsasantimicrobialcytotoxicagents AT sabryeman designsynthesisandpharmacologicalscreeningofbaminothiadiazolethiadiazinephosphonatebasedtriazolemotifsasantimicrobialcytotoxicagents |