Pal, K and Raza, MK and Legac, J and Ataur Rahman, M and Manzoor, S and Rosenthal, PJ and Hoda, N (2021) Design, synthesis, crystal structure and anti-plasmodial evaluation of tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives. In: RSC Medicinal Chemistry, 12 (6). pp. 970-981.
|
PDF
RSC_med_che_12-6_970-981_2021.pdf - Published Version Download (1MB) | Preview |
Abstract
Effective chemotherapy is essential for controlling malaria. However, resistance ofPlasmodium falciparumto existing antimalarial drugs has undermined attempts to control and eventually eradicate the disease. In this study, a series of 2-((substituted)(4-(5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-6-substitutedphenol derivatives were prepared using Petasis reaction with a view to evaluate their activities againstP. falciparum. The development of synthesized compounds (F1-F16) was justified through the study of H1NMR, C13NMR, mass spectra. CompoundF1andF2were also structurally validated by single crystal X-ray diffraction analysis. All the compounds were evaluated for theirin vitroantiplasmodial assessment against the W2 strain (chloroquine-resistant) ofP. falciparumIC50values ranging from 0.74-6.4 μM. Two compounds,F4andF16exhibited significant activity against W2 strain ofP. falciparumwith 0.75 and 0.74 μM. The compounds (F3-F6andF16) were also evaluated forin vitrocytotoxicity against two cancer cell lines, human lung (A549) and cervical (HeLa) cells, which demonstrated non-cytotoxicity with significant selectivity indices. In addition,in silicoADME profiling and physiochemical properties predicts drug-like properties with a very low toxic effect. Thus, all these results indicate that tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine scaffolds may serve as models for the development of antimalarial agents.
| Item Type: | Journal Article |
|---|---|
| Publication: | RSC Medicinal Chemistry |
| Publisher: | Royal Society of Chemistry |
| Additional Information: | The copyright for this article belongs to the Author. |
| Keywords: | 2 ((3 chloro 4 fluorophenyl)(4 (5,6,7,8 tetrahydrobenzo4,5thieno2,3 dpyrimidin 4 yl)piperazin 1 yl)methyl) 6 methoxyphenol; 2 ((3 chloro 4 fluorophenyl)(4 (5,6,7,8 tetrahydrobenzo4,5thieno2,3 dpyrimidin 4 yl)piperazin 1 yl)methyl)phenol; 2 ((3,4 dichlorophenyl)(4 (5,6,7,8 tetrahydrobenzo4,5thieno2,3 dpyrimidin 4 yl)piperazin 1 yl)methyl) 6 methoxyphenol; 2 ((3,4 dichlorophenyl)(4 (5,6,7,8 tetrahydrobenzo4,5thieno2,3 dpyrimidin 4 yl)piperazin 1 yl)methyl)phenol; 2 ((3,4 difluorophenyl)(4 (5,6,7,8 tetrahydrobenzo4,5thieno2,3 dpyrimidin 4 yl)piperazin 1 yl)methyl) 6 methoxyphenol; 2 ((3,4 difluorophenyl)(4 (5,6,7,8 tetrahydrobenzo4,5thieno2,3 dpyrimidin 4 yl)piperazin 1 yl)methyl)phenol; 2 ((4 (5,6,7,8 tetrahydrobenzo4,5thieno2,3 dpyrimidin 4 yl)piperazin 1 yl)(4 (trifluoro omethoxy)phenyl)methyl)phenol; 2 ((4 (5,6,7,8 tetrahydrobenzo4,5thieno2,3 dpyrimidin 4 yl)piperazin 1 yl)(p tolyl)methyl)phenol; 2 ((4 fluorophenyl)(4 (5,6,7,8 tetrahydrobenzo4,5thieno2,3 dpyrimidin 4 yl)piperazin 1 yl)methyl) 6 methoxyphenol; 2 ((4 fluorophenyl)(4 (5,6,7,8 tetrahydrobenzo4,5thieno2,3 dpyrimidin 4 yl)piperazin 1 yl)methyl)phenol; 2 ((4 methoxyphenyl)(4 (5,6,7,8 tetrahydrobenzo4,5thieno2,3 dpyrimidin 4 yl)piperazin 1 yl)methyl)phenol; 2 ((substituted)(4 (5,6,7,8tetrahydrobenzo4,5thieno2,3 dpyrimidin 4 yl)piperazin 1 yl)methyl) 6 substitutedphenol; 2 4 (5,6,7,8 tetrahydrobenzo4,5thieno2,3 dpyrimidin 4 yl)piperazin 1 yl)(4 (trifluoro omethyl)phenyl)methyl)phenol; 2 methoxy 6 ((4 (5,6,7,8 tetrahydrobenzo4,5thieno2,3 dpyrimidin 4 yl)piperazin 1 yl)(4 (trifluoromethyl)phenyl)methyl)phenol; 2 methoxy 6 ((4 (5,6,7,8 tetrahydrobenzo4,5thieno2,3 dpyrimidin 4 yl)piperazin 1 yl)(p tolyl)methyl)phenol; 2 methoxy 6 ((4 methoxyphenyl)(4 (5,6,7,8 tetrahydrobenzo4,5thieno2,3 dpyrimidin 4 yl)piperazin 1 yl)methyl)phenol; 2 methoxy 6 (4 (5,6,7,8 tetrahydrobenzo4,5thieno2,3 dpyrimidin 4 yl)piperazin 1 yl)(4 (trifluoromethoxy)phenyl)methyl)phenol; 4 (piperazin 1 yl) 5,6,7,8 tetrahydrobenzo4,5thieno2,3 dpyrimidine; 4 chloro 5,6,7,8 tetrahydrobenzo4,5thieno2,3 dpyrimidine; 5,6,7,8 tetrahydrobenzo4,5thieno2,3 dpyrimidin 4(3h) one; doxorubicin; ethyl 2 amino 4,5,6,7 tetrahydrobenzobthiophene 3 carboxylate; pyrimidine derivative; tetrahydrobenzo4,5thieno2,3 dpyrimidine derivative; unclassified drug, A-549 cell line; antineoplastic activity; antiplasmodial activity; Article; carbon nuclear magnetic resonance; chemical structure; controlled study; crystal structure; cytotoxicity; drug design; drug synthesis; elemental analysis; HeLa cell line; human; human cell; hydrogen bond; IC50; in vitro study; life cycle; lipophilicity; molecular docking; MTT assay; partition coefficient; physical chemistry; Plasmodium falciparum; protein fingerprinting; proton nuclear magnetic resonance; quantitative structure activity relation; spectrofluorometry; thin layer chromatography; X ray diffraction |
| Department/Centre: | Division of Chemical Sciences > Inorganic & Physical Chemistry |
| Date Deposited: | 07 Aug 2023 06:14 |
| Last Modified: | 07 Aug 2023 06:14 |
| URI: | https://eprints.iisc.ac.in/id/eprint/82826 |
Actions (login required)
 |
View Item |
