Synthesis and pharmacological evaluation of heteroarylamide derivatives as potential analgesic, anti-inflammatory, antidiarrheal and cytotoxic agents
Six heteroarylamide derivatives were synthesized in good yields and screened for several biological activities. Compounds 1–5 demonstrated analgesic activity with percentage inhibition of writhing between 77.10 and 95.79 %, comparable to that of the standard aceclofenac having 91.12 % writhing inhib...
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Elsevier
2024-12-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024166613 |
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| author | Nazifa Tabassum Sabiha Enam Spriha Poushali Saha Fahad Imtiaz Rahman A.S.M. Monjur Al Hossain S. M. Abdur Rahman |
| author_facet | Nazifa Tabassum Sabiha Enam Spriha Poushali Saha Fahad Imtiaz Rahman A.S.M. Monjur Al Hossain S. M. Abdur Rahman |
| author_sort | Nazifa Tabassum |
| collection | DOAJ |
| description | Six heteroarylamide derivatives were synthesized in good yields and screened for several biological activities. Compounds 1–5 demonstrated analgesic activity with percentage inhibition of writhing between 77.10 and 95.79 %, comparable to that of the standard aceclofenac having 91.12 % writhing inhibition. Evaluation of anti-inflammatory activity unveiled that compound 4 exhibited 36.9 %, 64.17 %, 82.9 % and 93.9 % inhibition of paw edema as compared to aceclofenac's inhibition of 35.5 %, 78.6 %, 79.3 % and 91.2 % at the 1st, 2nd, 3rd and 4th hours, respectively. Compounds 5 and 6 exerted considerable antidiarrheal effects with 85.00 % and 71.67 % inhibition of defecation at 25 mg/kg dose, respectively, whereas, the standard loperamide showed 85.00 % inhibition. Compounds 4–6 manifested promising activity in brine shrimp lethality bioassay as well as in trypan blue dye exclusion assay, resulting in 10–20 % cell viability on HeLa cell line and compound 5 was found to have the lowest IC50 of 281.96 μM in the MTT assay. Molecular docking analysis suggested that certain macromolecular targets such as cyclooxygenase-2, muscarinic M3 receptor and matrix metalloproteinase 9 (MMP9) might be involved for the observed activities. As predicted by in silico ADME/T analysis, the compounds also possessed good pharmacokinetic properties. |
| format | Article |
| id | doaj-art-2c39820f5d6e4d02b950762ca7c97c7a |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-2c39820f5d6e4d02b950762ca7c97c7a2024-12-13T10:59:17ZengElsevierHeliyon2405-84402024-12-011023e40630Synthesis and pharmacological evaluation of heteroarylamide derivatives as potential analgesic, anti-inflammatory, antidiarrheal and cytotoxic agentsNazifa Tabassum0Sabiha Enam Spriha1Poushali Saha2Fahad Imtiaz Rahman3A.S.M. Monjur Al Hossain4S. M. Abdur Rahman5Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, 1000, BangladeshDepartment of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, 1000, BangladeshDepartment of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, 1000, BangladeshDepartment of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, 1000, BangladeshDepartment of Pharmaceutical Technology, University of Dhaka, Dhaka, 1000, BangladeshDepartment of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, 1000, Bangladesh; Biomedical Research Center, University of Dhaka, Dhaka, 1000, Bangladesh; Corresponding author. Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, 1000, Bangladesh.Six heteroarylamide derivatives were synthesized in good yields and screened for several biological activities. Compounds 1–5 demonstrated analgesic activity with percentage inhibition of writhing between 77.10 and 95.79 %, comparable to that of the standard aceclofenac having 91.12 % writhing inhibition. Evaluation of anti-inflammatory activity unveiled that compound 4 exhibited 36.9 %, 64.17 %, 82.9 % and 93.9 % inhibition of paw edema as compared to aceclofenac's inhibition of 35.5 %, 78.6 %, 79.3 % and 91.2 % at the 1st, 2nd, 3rd and 4th hours, respectively. Compounds 5 and 6 exerted considerable antidiarrheal effects with 85.00 % and 71.67 % inhibition of defecation at 25 mg/kg dose, respectively, whereas, the standard loperamide showed 85.00 % inhibition. Compounds 4–6 manifested promising activity in brine shrimp lethality bioassay as well as in trypan blue dye exclusion assay, resulting in 10–20 % cell viability on HeLa cell line and compound 5 was found to have the lowest IC50 of 281.96 μM in the MTT assay. Molecular docking analysis suggested that certain macromolecular targets such as cyclooxygenase-2, muscarinic M3 receptor and matrix metalloproteinase 9 (MMP9) might be involved for the observed activities. As predicted by in silico ADME/T analysis, the compounds also possessed good pharmacokinetic properties.http://www.sciencedirect.com/science/article/pii/S2405844024166613AntidiarrhealCytotoxicHeteroarylamidesSynthesisPeripheral analgesic |
| spellingShingle | Nazifa Tabassum Sabiha Enam Spriha Poushali Saha Fahad Imtiaz Rahman A.S.M. Monjur Al Hossain S. M. Abdur Rahman Synthesis and pharmacological evaluation of heteroarylamide derivatives as potential analgesic, anti-inflammatory, antidiarrheal and cytotoxic agents Heliyon Antidiarrheal Cytotoxic Heteroarylamides Synthesis Peripheral analgesic |
| title | Synthesis and pharmacological evaluation of heteroarylamide derivatives as potential analgesic, anti-inflammatory, antidiarrheal and cytotoxic agents |
| title_full | Synthesis and pharmacological evaluation of heteroarylamide derivatives as potential analgesic, anti-inflammatory, antidiarrheal and cytotoxic agents |
| title_fullStr | Synthesis and pharmacological evaluation of heteroarylamide derivatives as potential analgesic, anti-inflammatory, antidiarrheal and cytotoxic agents |
| title_full_unstemmed | Synthesis and pharmacological evaluation of heteroarylamide derivatives as potential analgesic, anti-inflammatory, antidiarrheal and cytotoxic agents |
| title_short | Synthesis and pharmacological evaluation of heteroarylamide derivatives as potential analgesic, anti-inflammatory, antidiarrheal and cytotoxic agents |
| title_sort | synthesis and pharmacological evaluation of heteroarylamide derivatives as potential analgesic anti inflammatory antidiarrheal and cytotoxic agents |
| topic | Antidiarrheal Cytotoxic Heteroarylamides Synthesis Peripheral analgesic |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024166613 |
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