title: Ultrasound Mediated One-Pot, Three Component Synthesis, Docking and ADME Prediction of Novel 5-Amino-2-(4-chlorophenyl)-7-Substituted Phenyl-8,8a-dihydro-7H-(1,3,4)thiadiazolo(3,2-α)pyrimidine-6-carbonitrile Derivatives as Anticancer Agents.
abstract: Herein, we report an environmentally friendly, rapid, and convenient one-pot ultrasound-promoted synthesis of 5-amino-2-(4-chlorophenyl)-7-substituted phenyl-8,8a-dihydro-7H-(1,3,4)thiadiazolo(3,2-α)pyrimidine-6-carbonitrile derivatives. The in-vitro anticancer activities of these compounds were evaluated against four human tumor cell lines. Among all the synthesized derivatives, compound 4i, which has substituent 3-hydroxy-4-methoxyphenyl is found to have the highest GI50 value of 32.7 μM, 55.3 μM, 34.3 μM, 28.9 μM for MCF-7, K562, HeLa and PC-3 cancer cell lines respectively. A docking study of the newly synthesized compounds were performed, and the results showed good binding mode in the active site of thymidylate synthase enzyme. ADME properties of synthesized compounds were also studied and showed good drug like properties.
authors.affiliation: Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Rauza Baug, Aurangabad, Maharashtra 431001, India. shailee2010@gmail.com.
authors.forename: Shailee V
authors.initials: SV
authors.lastname: Tiwari
authors.affiliation: Departamento de Qu&#237;mica Org&#225;nica, Facultad de Ciencias, Universidad of Santiago De Compostela, Alfonso X el Sabio, Lugo 27002, Spain. julioa.seijas@usc.es.
authors.forename: Julio A
authors.initials: JA
authors.lastname: Seijas
authors.affiliation: Departamento de Qu&#237;mica Org&#225;nica, Facultad de Ciencias, Universidad of Santiago De Compostela, Alfonso X el Sabio, Lugo 27002, Spain. pilar.vazquez.tato@usc.es.
authors.forename: M Pilar
authors.initials: MP
authors.lastname: Vazquez-Tato
authors.affiliation: Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra 431004, India. aniketpharma1@gmail.com.
authors.forename: Aniket P
authors.initials: AP
authors.lastname: Sarkate
authors.affiliation: Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra 431004, India. dklokwani@gmail.com.
authors.forename: Deepak K
authors.initials: DK
authors.lastname: Lokwani
authors.affiliation: Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Rauza Baug, Aurangabad, Maharashtra 431001, India. annapratimanikalje@gmail.com.
authors.forename: Anna Pratima G
authors.initials: AP
authors.lastname: Nikalje
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*; D000069453:Ultrasonic Waves
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D009570:Nitriles; D013940:Thymidylate Synthase
keywords: 1,3,4-thiadiazolo(3,2-α)pyrimidine; ADME; docking; ultrasound-promoted synthesis