{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T01:56:16Z","timestamp":1782698176530,"version":"3.54.5"},"reference-count":36,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T00:00:00Z","timestamp":1658793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research, King Saud University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Piperazine-based dithiocarbamates serve as important scaffolds for numerous pharmacologically active drugs. The current study investigates the design and synthesis of a series of dithiocarbamates with a piperazine unit as well as their biological activities. Under ultrasound conditions, the corresponding piperazine-1-carbodithioates 5a\u20135j were synthesized from monosubstituted piperazine 2 and N-phenylacetamides 4a\u20134j in the presence of sodium acetate and carbon disulfide in methanol. The structures of the newly synthesized piperazines were confirmed, and their anti-lung carcinoma effects were evaluated. A cytotoxic assay was performed to assess the hemolytic and thrombolytic potential of the synthesized piperazines 5a\u20135j. The types of substituents on the aryl ring were found to affect the anticancer activity of piperazines 5a\u20135j. Piperazines containing 2-chlorophenyl (5b; cell viability = 25.11 \u00b1 2.49) and 2,4-dimethylphenyl (5i; cell viability = 25.31 \u00b1 3.62) moieties demonstrated the most potent antiproliferative activity. On the other hand, piperazines containing 3,4-dichlorophenyl (5d; 0.1%) and 3,4-dimethylphenyl (5j; 0.1%) rings demonstrated the least cytotoxicity. The piperazine with the 2,5-dimethoxyphenyl moiety (5h; 60.2%) showed the best thrombolytic effect. To determine the mode of binding, in silico modeling of the most potent piperazine (i.e., 5b) was performed, and the results were in accordance with those of antiproliferation. It exhibits a similar binding affinity to PQ10 and an efficient conformational alignment with the lipophilic site of PDE10A conserved for PQ10A.<\/jats:p>","DOI":"10.3390\/molecules27154776","type":"journal-article","created":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T04:59:16Z","timestamp":1658897956000},"page":"4776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Ultrasound-Assisted Synthesis and In Silico Modeling of Methanesulfonyl-Piperazine-Based Dithiocarbamates as Potential Anticancer, Thrombolytic, and Hemolytic Structural Motifs"],"prefix":"10.3390","volume":"27","author":[{"given":"Freeha","family":"Hafeez","sequence":"first","affiliation":[{"name":"Department of Chemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2127-8848","authenticated-orcid":false,"given":"Ameer Fawad","family":"Zahoor","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9669-7364","authenticated-orcid":false,"given":"Azhar","family":"Rasul","sequence":"additional","affiliation":[{"name":"Department of Zoology, Government College University Faisalabad, Faisalabad 38000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5659-0562","authenticated-orcid":false,"given":"Asim","family":"Mansha","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razia","family":"Noreen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7789-4530","authenticated-orcid":false,"given":"Zohaib","family":"Raza","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Government College University Faisalabad, Faisalabad 38000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kulsoom Ghulam","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8977-3303","authenticated-orcid":false,"given":"Ali","family":"Irfan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6675-3126","authenticated-orcid":false,"given":"Gamal A.","family":"El-Hiti","sequence":"additional","affiliation":[{"name":"Cornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21S","DOI":"10.1378\/chest.123.1_suppl.21S","article-title":"Epidemiology of lung cancer","volume":"123","author":"Alberg","year":"2003","journal-title":"Chest"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1164\/rccm.200504-531OE","article-title":"One hundred years of lung cancer","volume":"172","author":"Spiro","year":"2005","journal-title":"Am. 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