6-Amino-4-aryl-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamides: Synthesis, Biological Activity, Quantum Chemical Studies and In Silico Docking Studies
New [1,2]dithiolo[3,4-b]pyridine-5-carboxamides were synthesized through the reaction of dithiomalondianilide (N,N′-diphenyldithiomalondiamide) with 3-aryl-2-cyanoacrylamides or via a three-component reaction involving aromatic aldehydes, cyanoacetamide and dithiomalondianilide in the presence of mo...
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| Format: | Article |
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/2/769 |
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| author | Victor V. Dotsenko Alexander V. Bespalov Anna E. Sinotsko Azamat Z. Temerdashev Vladimir K. Vasilin Ekaterina A. Varzieva Vladimir D. Strelkov Nicolai A. Aksenov Inna V. Aksenova |
| author_facet | Victor V. Dotsenko Alexander V. Bespalov Anna E. Sinotsko Azamat Z. Temerdashev Vladimir K. Vasilin Ekaterina A. Varzieva Vladimir D. Strelkov Nicolai A. Aksenov Inna V. Aksenova |
| author_sort | Victor V. Dotsenko |
| collection | DOAJ |
| description | New [1,2]dithiolo[3,4-b]pyridine-5-carboxamides were synthesized through the reaction of dithiomalondianilide (N,N′-diphenyldithiomalondiamide) with 3-aryl-2-cyanoacrylamides or via a three-component reaction involving aromatic aldehydes, cyanoacetamide and dithiomalondianilide in the presence of morpholine. The structure of 6-amino-4-(2,4-dichloro- phenyl)-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamide was confirmed using X-ray crystallography. To understand the reaction mechanism in detail, density functional theory (DFT) calculations were performed with a Grimme B97-3c composite computational scheme. The results revealed that the rate-limiting step is a cyclization process leading to the closure of the 1,4-dihydropyridine ring, with an activation barrier of 28.8 kcal/mol. Some of the dithiolo[3,4-b]pyridines exhibited moderate herbicide safening effects against 2,4-D. Additionally, ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) parameters were calculated and molecular docking studies were performed to identify potential protein targets. |
| first_indexed | 2024-03-08T09:53:50Z |
| format | Article |
| id | doaj.art-719095cd00f1491190dc6fb6e0c904d7 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T09:53:50Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-719095cd00f1491190dc6fb6e0c904d72024-01-29T13:54:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-0125276910.3390/ijms250207696-Amino-4-aryl-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamides: Synthesis, Biological Activity, Quantum Chemical Studies and In Silico Docking StudiesVictor V. Dotsenko0Alexander V. Bespalov1Anna E. Sinotsko2Azamat Z. Temerdashev3Vladimir K. Vasilin4Ekaterina A. Varzieva5Vladimir D. Strelkov6Nicolai A. Aksenov7Inna V. Aksenova8Department of Organic Chemistry and Technologies, Kuban State University, 149 Stavropolskaya St., 350040 Krasnodar, RussiaDepartment of Organic Chemistry and Technologies, Kuban State University, 149 Stavropolskaya St., 350040 Krasnodar, RussiaDepartment of Organic Chemistry and Technologies, Kuban State University, 149 Stavropolskaya St., 350040 Krasnodar, RussiaDepartment of Analytical Chemistry, Kuban State University, 149 Stavropolskaya St., 350040 Krasnodar, RussiaDepartment of Bioorganic Chemistry, Kuban State Technological University, 2 Moskovskaya St., 350072 Krasnodar, RussiaDepartment of Organic Chemistry and Technologies, Kuban State University, 149 Stavropolskaya St., 350040 Krasnodar, RussiaDepartment of Organic Chemistry and Technologies, Kuban State University, 149 Stavropolskaya St., 350040 Krasnodar, RussiaDepartment of Chemistry, North Caucasus Federal University, 1a Pushkin St., 355017 Stavropol, RussiaDepartment of Chemistry, North Caucasus Federal University, 1a Pushkin St., 355017 Stavropol, RussiaNew [1,2]dithiolo[3,4-b]pyridine-5-carboxamides were synthesized through the reaction of dithiomalondianilide (N,N′-diphenyldithiomalondiamide) with 3-aryl-2-cyanoacrylamides or via a three-component reaction involving aromatic aldehydes, cyanoacetamide and dithiomalondianilide in the presence of morpholine. The structure of 6-amino-4-(2,4-dichloro- phenyl)-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamide was confirmed using X-ray crystallography. To understand the reaction mechanism in detail, density functional theory (DFT) calculations were performed with a Grimme B97-3c composite computational scheme. The results revealed that the rate-limiting step is a cyclization process leading to the closure of the 1,4-dihydropyridine ring, with an activation barrier of 28.8 kcal/mol. Some of the dithiolo[3,4-b]pyridines exhibited moderate herbicide safening effects against 2,4-D. Additionally, ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) parameters were calculated and molecular docking studies were performed to identify potential protein targets.https://www.mdpi.com/1422-0067/25/2/769heterocyclizationMichael additiondithiomalondiamidesdithiolo[3,4-b]pyridinesDFT calculationsreaction mechanism studies |
| spellingShingle | Victor V. Dotsenko Alexander V. Bespalov Anna E. Sinotsko Azamat Z. Temerdashev Vladimir K. Vasilin Ekaterina A. Varzieva Vladimir D. Strelkov Nicolai A. Aksenov Inna V. Aksenova 6-Amino-4-aryl-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamides: Synthesis, Biological Activity, Quantum Chemical Studies and In Silico Docking Studies International Journal of Molecular Sciences heterocyclization Michael addition dithiomalondiamides dithiolo[3,4-b]pyridines DFT calculations reaction mechanism studies |
| title | 6-Amino-4-aryl-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamides: Synthesis, Biological Activity, Quantum Chemical Studies and In Silico Docking Studies |
| title_full | 6-Amino-4-aryl-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamides: Synthesis, Biological Activity, Quantum Chemical Studies and In Silico Docking Studies |
| title_fullStr | 6-Amino-4-aryl-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamides: Synthesis, Biological Activity, Quantum Chemical Studies and In Silico Docking Studies |
| title_full_unstemmed | 6-Amino-4-aryl-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamides: Synthesis, Biological Activity, Quantum Chemical Studies and In Silico Docking Studies |
| title_short | 6-Amino-4-aryl-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamides: Synthesis, Biological Activity, Quantum Chemical Studies and In Silico Docking Studies |
| title_sort | 6 amino 4 aryl 7 phenyl 3 phenylimino 4 7 dihydro 3h 1 2 dithiolo 3 4 b pyridine 5 carboxamides synthesis biological activity quantum chemical studies and in silico docking studies |
| topic | heterocyclization Michael addition dithiomalondiamides dithiolo[3,4-b]pyridines DFT calculations reaction mechanism studies |
| url | https://www.mdpi.com/1422-0067/25/2/769 |
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