An ultrasound assisted, ionic liquid-molecular iodine synergy driven efficient green synthesis of pyrrolobenzodiazepine-triazole hybrids as potential anticancer agents
Herein, we report an efficient and eco-friendly, ultrasound assisted synthetic strategy for the construction of diversified pyrrolobenzodiazepine-triazole hybrids, which are potentially pharmaceutically important scaffolds, via a domino reaction involving intermolecular electrophilic substitution fo...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-05-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1168566/full |
| _version_ | 1797833135180742656 |
|---|---|
| author | Mohammad Saquib Shakir Ahamad Mohammad Faheem Khan Mohammad Imran Khan Mohammad Imran Khan Mohd Kamil Hussain Mohd Kamil Hussain |
| author_facet | Mohammad Saquib Shakir Ahamad Mohammad Faheem Khan Mohammad Imran Khan Mohammad Imran Khan Mohd Kamil Hussain Mohd Kamil Hussain |
| author_sort | Mohammad Saquib |
| collection | DOAJ |
| description | Herein, we report an efficient and eco-friendly, ultrasound assisted synthetic strategy for the construction of diversified pyrrolobenzodiazepine-triazole hybrids, which are potentially pharmaceutically important scaffolds, via a domino reaction involving intermolecular electrophilic substitution followed by intramolecular Huisgen 1,3-dipolar azide-alkyne cycloaddition. The USP of the reported protocol is the use of benign and inexpensive, recyclable molecular iodine-ionic liquid synergistic catalytic system cum reaction media for achieving the synthesis. The other salient features of this method are the use of mild reaction conditions, high yield and atom economy, operational simplicity, broad substrate scope and easy workup and purification. All the synthesized compounds were evaluated for in vitro anti-proliferative activity against various cancer cell lines. From among the synthesized title compounds, 9,9-dimethyl-8-phenyl-9H-benzo [b]pyrrolo [1,2-d][1,2,3]triazolo[5,1-g][1,4]diazepine (7) was found most to be the most active compound exhibiting IC50 value of 6.60, 5.45, 7.85, 11.21, 12.24, 10.12, and 11.32 µM against MCF-7, MDA-MB-231, HeLa, SKOV-3, A549, HCT-116 and DLD-1 cell lines, respectively. Further the compounds were found to be non-toxic against normal human embryonic kidney (HEK-293) cell line. |
| first_indexed | 2024-04-09T14:18:40Z |
| format | Article |
| id | doaj.art-9c81804d25034c32a3db4f25b04ad27b |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-09T14:18:40Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-9c81804d25034c32a3db4f25b04ad27b2023-05-05T04:45:35ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-05-011410.3389/fphar.2023.11685661168566An ultrasound assisted, ionic liquid-molecular iodine synergy driven efficient green synthesis of pyrrolobenzodiazepine-triazole hybrids as potential anticancer agentsMohammad Saquib0Shakir Ahamad1Mohammad Faheem Khan2Mohammad Imran Khan3Mohammad Imran Khan4Mohd Kamil Hussain5Mohd Kamil Hussain6Department of Chemistry, University of Allahabad, Prayagraj, Uttar Pradesh, IndiaDepartment of Chemistry, Aligarh Muslim University, Aligarh, Uttar Pradesh, IndiaDepartment of Biotechnology, Era’s Lucknow Medical College, Era University, Lucknow, Uttar Pradesh, IndiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi ArabiaCentre of Artificial Intelligence in Precision Medicine, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Chemistry, Govt. Raza P.G. College, Rampur, Uttar Pradesh, IndiaM.J.P Rohilkahand University, Bareilly, Uttar Pradesh, IndiaHerein, we report an efficient and eco-friendly, ultrasound assisted synthetic strategy for the construction of diversified pyrrolobenzodiazepine-triazole hybrids, which are potentially pharmaceutically important scaffolds, via a domino reaction involving intermolecular electrophilic substitution followed by intramolecular Huisgen 1,3-dipolar azide-alkyne cycloaddition. The USP of the reported protocol is the use of benign and inexpensive, recyclable molecular iodine-ionic liquid synergistic catalytic system cum reaction media for achieving the synthesis. The other salient features of this method are the use of mild reaction conditions, high yield and atom economy, operational simplicity, broad substrate scope and easy workup and purification. All the synthesized compounds were evaluated for in vitro anti-proliferative activity against various cancer cell lines. From among the synthesized title compounds, 9,9-dimethyl-8-phenyl-9H-benzo [b]pyrrolo [1,2-d][1,2,3]triazolo[5,1-g][1,4]diazepine (7) was found most to be the most active compound exhibiting IC50 value of 6.60, 5.45, 7.85, 11.21, 12.24, 10.12, and 11.32 µM against MCF-7, MDA-MB-231, HeLa, SKOV-3, A549, HCT-116 and DLD-1 cell lines, respectively. Further the compounds were found to be non-toxic against normal human embryonic kidney (HEK-293) cell line.https://www.frontiersin.org/articles/10.3389/fphar.2023.1168566/fullpyrrolobenzodiazepine-triazole hybridsionic liquidiodinegreen synthesisanti-cancer agents |
| spellingShingle | Mohammad Saquib Shakir Ahamad Mohammad Faheem Khan Mohammad Imran Khan Mohammad Imran Khan Mohd Kamil Hussain Mohd Kamil Hussain An ultrasound assisted, ionic liquid-molecular iodine synergy driven efficient green synthesis of pyrrolobenzodiazepine-triazole hybrids as potential anticancer agents Frontiers in Pharmacology pyrrolobenzodiazepine-triazole hybrids ionic liquid iodine green synthesis anti-cancer agents |
| title | An ultrasound assisted, ionic liquid-molecular iodine synergy driven efficient green synthesis of pyrrolobenzodiazepine-triazole hybrids as potential anticancer agents |
| title_full | An ultrasound assisted, ionic liquid-molecular iodine synergy driven efficient green synthesis of pyrrolobenzodiazepine-triazole hybrids as potential anticancer agents |
| title_fullStr | An ultrasound assisted, ionic liquid-molecular iodine synergy driven efficient green synthesis of pyrrolobenzodiazepine-triazole hybrids as potential anticancer agents |
| title_full_unstemmed | An ultrasound assisted, ionic liquid-molecular iodine synergy driven efficient green synthesis of pyrrolobenzodiazepine-triazole hybrids as potential anticancer agents |
| title_short | An ultrasound assisted, ionic liquid-molecular iodine synergy driven efficient green synthesis of pyrrolobenzodiazepine-triazole hybrids as potential anticancer agents |
| title_sort | ultrasound assisted ionic liquid molecular iodine synergy driven efficient green synthesis of pyrrolobenzodiazepine triazole hybrids as potential anticancer agents |
| topic | pyrrolobenzodiazepine-triazole hybrids ionic liquid iodine green synthesis anti-cancer agents |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1168566/full |
| work_keys_str_mv | AT mohammadsaquib anultrasoundassistedionicliquidmoleculariodinesynergydrivenefficientgreensynthesisofpyrrolobenzodiazepinetriazolehybridsaspotentialanticanceragents AT shakirahamad anultrasoundassistedionicliquidmoleculariodinesynergydrivenefficientgreensynthesisofpyrrolobenzodiazepinetriazolehybridsaspotentialanticanceragents AT mohammadfaheemkhan anultrasoundassistedionicliquidmoleculariodinesynergydrivenefficientgreensynthesisofpyrrolobenzodiazepinetriazolehybridsaspotentialanticanceragents AT mohammadimrankhan anultrasoundassistedionicliquidmoleculariodinesynergydrivenefficientgreensynthesisofpyrrolobenzodiazepinetriazolehybridsaspotentialanticanceragents AT mohammadimrankhan anultrasoundassistedionicliquidmoleculariodinesynergydrivenefficientgreensynthesisofpyrrolobenzodiazepinetriazolehybridsaspotentialanticanceragents AT mohdkamilhussain anultrasoundassistedionicliquidmoleculariodinesynergydrivenefficientgreensynthesisofpyrrolobenzodiazepinetriazolehybridsaspotentialanticanceragents AT mohdkamilhussain anultrasoundassistedionicliquidmoleculariodinesynergydrivenefficientgreensynthesisofpyrrolobenzodiazepinetriazolehybridsaspotentialanticanceragents AT mohammadsaquib ultrasoundassistedionicliquidmoleculariodinesynergydrivenefficientgreensynthesisofpyrrolobenzodiazepinetriazolehybridsaspotentialanticanceragents AT shakirahamad ultrasoundassistedionicliquidmoleculariodinesynergydrivenefficientgreensynthesisofpyrrolobenzodiazepinetriazolehybridsaspotentialanticanceragents AT mohammadfaheemkhan ultrasoundassistedionicliquidmoleculariodinesynergydrivenefficientgreensynthesisofpyrrolobenzodiazepinetriazolehybridsaspotentialanticanceragents AT mohammadimrankhan ultrasoundassistedionicliquidmoleculariodinesynergydrivenefficientgreensynthesisofpyrrolobenzodiazepinetriazolehybridsaspotentialanticanceragents AT mohammadimrankhan ultrasoundassistedionicliquidmoleculariodinesynergydrivenefficientgreensynthesisofpyrrolobenzodiazepinetriazolehybridsaspotentialanticanceragents AT mohdkamilhussain ultrasoundassistedionicliquidmoleculariodinesynergydrivenefficientgreensynthesisofpyrrolobenzodiazepinetriazolehybridsaspotentialanticanceragents AT mohdkamilhussain ultrasoundassistedionicliquidmoleculariodinesynergydrivenefficientgreensynthesisofpyrrolobenzodiazepinetriazolehybridsaspotentialanticanceragents |