Mechanistic elucidation and prediction of the anticancer activity of 1,3,4-thiadiazol-2-amide derivatives

Abstract: A series of novel amide and Schiffs base functionalized novel pyrido[1,2-a]pyrimidin-4-one derivatives were prepared starting from 6-(thiophene-2-yl)/phenyl-4-(trifluoromethyl) pyridin-2-amine 1a and 1b. These compounds on reaction with EMME, to afford compounds 2a and 2b, followed by cyclization to afford compounds 3a and 3b. Treatment of compound 3a and 3b with hydrazine hydrate to get compounds 4a and 4b, compounds 4a and 4b on reaction with different substituted aromatic aldehydes to get Schiff’s base derivatives 5a-j, in another way compounds 3a, 3b on reaction with aliphatic amines to get amide derivatives 6a-f. All the compounds 5a-j and 6a-f were screened against four human cancer cell lines (HeLa, COLO205, Hep G2, and MCF 7), among all the derivatives, compounds 5c, 5e, 6a, and 6b showed promising anticancer activity.

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Design, Synthesis, Anticancer Evaluation, and Molecular Docking Studies of Novel Benzoxazole Linked 1,3,4-Oxadiazoles

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666210706120203 ◽

2021 ◽

Vol 21 ◽

Author(s):

Sushmitha Bujji ◽

Praveen Kumar E ◽

Sree Kanth Sivan ◽

Manjunatha DH ◽

Subhashini N.J.P.

Keyword(s):

Molecular Docking ◽

Anticancer Activity ◽

Cell Lines ◽

Research Work ◽

Docking Simulation ◽

Research Field ◽

Spectroscopic Techniques ◽

Cancer Disease ◽

Amide Derivatives

Background: Cancer disease is making a serious concern globally. Global cancer occurrence is steadily increasing every year. There is always a persistent need to develop new anticancer drugs with reduced side effects or act synergistically with the existing chemotherapeutics. Objective: Benzoxazoles are fused bicyclic nitrogen and oxygen-containing heterocyclic compounds and are considered biologically privileged scaffolds. We designed a synthetic route to link the benzoxazoles with oxadiazoles resulting in a better pharmacophore for anticancer activity. Methods: A series of novel amide derivatives of benzoxazole linked 1,3,4-oxadiazoles (10a-j) were synthesized and characterized by 1H NMR, 13C NMR, and mass spectroscopic techniques. The biological properties of the compounds were screened in vitro against four different tumor cell lines. Results: The results suggest that the compound 10b having 3,4,5-trimethoxy substitution on the phenyl ring exhibited potent anticancer activity in three cell lines (A549 = 0.13 ± 0.014 µM, MCF-7 = 0.10 ± 0.013 µM and HT-29 = 0.22 ± 0.017 µM). Notably, among the synthesized derivatives, compounds 10b, 10c, 10f, 10g, and 10i exhibited potent anticancer activity than the control IC50 in the range of 0.11 ± 0.02 to 0.93 ± 0.034 µM. Molecular docking simulation results showed compounds were stabilized by hydrogen bond and π-π interactions with the protein. Conclusion: The molecules showed comparable binding affinities with standard Combretastatin-A4. The present research work is preliminary and needs further studies to take the synthesized compounds to the next level in the cancer research field.

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4-Aminopyridine based amide derivatives as dual inhibitors of tissue non-specific alkaline phosphatase and ecto-5′-nucleotidase with potential anticancer activity

Bioorganic Chemistry ◽

10.1016/j.bioorg.2017.11.013 ◽

2018 ◽

Vol 76 ◽

pp. 237-248 ◽

Cited By ~ 10

Author(s):

Sidra Hassan ◽

Syeda Abida Ejaz ◽

Aamer Saeed ◽

Muddasar Shehzad ◽

Shafi Ullah Khan ◽

...

Keyword(s):

Alkaline Phosphatase ◽

Anticancer Activity ◽

Specific Alkaline Phosphatase ◽

Amide Derivatives ◽

Dual Inhibitors

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Synthesis and Anticancer Activity of Novel Hetero Ring Fused Pyridine Amide Derivatives

Asian Journal of Chemistry ◽

10.14233/ajchem.2019.22150 ◽

2019 ◽

Vol 31 (11) ◽

pp. 2485-2491

Author(s):

Hanumandlu Racha ◽

Balakishan Vadla ◽

Kavitha Peddolla ◽

Sailu Betala

Keyword(s):

Anticancer Activity ◽

Normal Cell ◽

Aromatic Aldehydes ◽

Kidney Cells ◽

Human Embryonic Kidney ◽

Human Embryonic Kidney Cells ◽

Normal Cell Line ◽

Amide Derivatives ◽

A549 Lung ◽

Mcf 7

A series of novel hetero ring fused pyridine amide derivatives were prepared starting from ethyl furo[2,3-b]pyridine-2-carboxylate (3) on reaction with ammonia to afford furo[2,3-b]pyridine-2-carboxamide (4), compound 4 on reaction with trifluoroacetic acid to give compound 5, which on reaction with bromoethyl acetate followed by hydrazine hydrate to give compound 7. Compound 7 when reacted with different substituted aromatic aldehydes to give Schiff base compounds (8a-l). Similarly, compound 6a when reacted with diverse substituted aliphatic amines to give amide derivatives (9a-h). All the synthesized compounds 8a-l and 9a-h were screened for anticancer activity against four cancer cell lines such as A549-lung cancer (CCL-185); DU145-prostate cancer (HTB-81); SiHa-squamous cell carcinoma (HTB-35); MCF-7-breast cancer (HTB-22); HEK-29-human embryonic kidney cells (CRL-1573). Compounds 9e and 9f are found to have promising anticancer activity at micro molar concentration and found to be non-toxic on normal cell line.

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Synthesis and anticancer activity of novel amide derivatives of non-acetal deoxoartemisinin

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2009.09.093 ◽

2009 ◽

Vol 19 (22) ◽

pp. 6303-6306 ◽

Cited By ~ 14

Author(s):

Mankil Jung ◽

Namsoo Park ◽

Hyung-In Moon ◽

Yongnam Lee ◽

Won-Yoon Chung ◽

...

Keyword(s):

Anticancer Activity ◽

Amide Derivatives ◽

Derivatives Of

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Synthesis of Novel Amide Functionalized Pyrido[2,3-d]pyrimidine Derivatives and their Anticancer Activity

Asian Journal of Chemistry ◽

10.14233/ajchem.2021.23225 ◽

2021 ◽

Vol 33 (7) ◽

pp. 1579-1584

Author(s):

Chiranjeevi Abba ◽

Naveen Puram ◽

Sailu Betala

Keyword(s):

Anticancer Activity ◽

Human Cancer ◽

Aromatic Aldehydes ◽

Pyrimidine Derivatives ◽

Human Cancer Cell Lines ◽

Schiff Base Derivatives ◽

Amide Derivatives ◽

Anti Cancer ◽

A549 Lung ◽

Cancer Activity

A series of novel amide functionalized pyrido[2,3-d]pyrimidine derivatives were synthesized from 2-amino-6-(thiophen-2-yl)-4-(trifluoro-methyl)nicotinonitrile (1), which on reaction with trifluoroacetic acid to get pyridopyrimidine (2). Compound 2 when treated with bromoethyl acetate followed by hydrazine hydrate to get hydrazide derivatives 4. Compound 4 on reaction with different substituted aromatic aldehydes to obtain Schiff base derivatives 5a-f. In another way, compound 3 treated with different substituted amines and amino acids to obtain amide derivatives 6a-f, 7a-d and 8a-c. All the compounds evaluated for anti-cancer activity against four human cancer cell lines such as A549-Lung cancer (CCL-185), MCF7-Breast cancer (HTB-22), DU145-prostate cancer (HTB-81) and HeLa-cervical cancer (CCL-2) and among the sythesized compounds, only 5d, 7d and 8a were identified as the potent compounds against the anticancer activity.

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