Coumarin-Pyrazole Linked Carbodithioates as Potential Anti-Сancer Agents: Design, Synthesis, Biological, and Molecular Docking Investigation

Akki, Mahesh; Reddy, D. Narasimha; Katagi, Kariyappa S.; Kumar, Amit; Babagond, Vardhaman; Munnolli, Ravindra S.; Joshi, Shrinivas D.

doi:10.1134/s1070363222100231

Cited by 7 publications

(1 citation statement)

References 57 publications

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“…In 2020 lung cancer claimed about 1.80 million lives and affected over 2.21 million people globally making it the most common and deadly disease worldwide. Conversely breast cancer, the leading type among women caused an estimated 685,000 deaths and affected nearly 2.26 million individuals globally the same year [2a,b] . Chemotherapy, radiotherapy, and surgery are key cancer treatment options.…”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of Potent Anticancer Agents Using Coumarin‐Quinazolinone Based Scaffolds: Exploration of ADME Properties and Molecular Docking Studies

Babagond,

Katagi,

Akki

et al. 2024

ChemistrySelect

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Cancer remains a complex global threat causing widespread deaths. Developing effective anticancer agents despite advancements still remained challenging. In this work it is designed and synthesised therapeutically active anticancer agents based on coumarin‐quinazolinone 5(a–j) through nucleophilic substitution reaction of 4‐bromomethyl coumarin derivatives with 6,7‐bis(2‐methoxyethoxy)quinazolin‐4(3H)‐one and characterised by using FTIR, 1HNMR, 13C NMR and LCMS analysis. The compounds 5(a–j) were screened for in vitro anticancer activity against A‐549 lung cancer cell lines and MDA‐MB‐231 cell lines. Compound 5i emerged as the most promising antiproliferative candidate demonstrating an IC50 value of 7.11 μM against A‐549 cell lines. Meanwhile compound 5g found as a hit candidate in the case of MDA‐MB‐231, exhibiting an IC50 of 5.12 μM, surpassing the potency of the standard drug doxorubicin (IC50 5.89 μM). Further, the safety profile of coumarin‐quinazolinone scafolds (5a–j) were examined for their cytotoxicity towards human embryonic kidney cell lines (HEK293). It was found that the most active compounds exhibited good safety profile towards human embryonic cell lines. Additionally, molecular docking investigations confirmed that compounds 5(a–j) exhibited elevated docking scores and demonstrated favourable interactions with the HER2 (PDB:3PP0) and VEGFR2 (PDB:4ASE). Furthermore, we investigated the ADME properties using the SwissADME tool.

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Section: Introductionmentioning

confidence: 99%

Design and Synthesis of Potent Anticancer Agents Using Coumarin‐Quinazolinone Based Scaffolds: Exploration of ADME Properties and Molecular Docking Studies

Babagond,

Katagi,

Akki

et al. 2024

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Design, synthesis, molecular docking, and biological evaluation of coumarin‐thymidine analogs as potent anti‐TB agents

Reddy

Sinha

Kurjogi

et al. 2023

Archiv der Pharmazie

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With the intent to discover new antituberculosis (TB) compounds, coumarinthymidine analogs were synthesized using second-order nucleophilic substitution reactions of bromomethyl coumarin with thymidine. The newly synthesized coumarin-thymidine conjugates (1a-l) were characterized using IR, NMR, GC-MS, and CHN elemental analysis. The novel conjugates were found to exhibit potent anti-TB activity against the Mycobacterium tuberculosis H 37 Rv strain, with minimum inhibitory concentrations (MIC) of the active compounds ranging between 0.012 and 0.482 µM. Compound 1k was established as the most active candidate with a MIC of 0.012 µM. The toxicity study on HEK cells confirmed the nontoxic nature of compounds 1e, 1h, 1i, 1j, and 1k. Also, the most active compounds (1k, 1j, and 1e) were stable in the pH range from 2.5 to 10, indicating compatibility with the biophysical environment. Based on the pK a studies, compounds 1k, 1j, and 1e are capable of crossing lipid-membrane barriers and acting on target cells. Molecular docking studies on the M. tuberculosis β-oxidation trifunctional enzyme (PDB ID: 7O4V) were conducted to investigate the mechanisms of anti-TB activity. All compounds showed excellent hydrogen binding interactions and exceptional docking scores against M. tuberculosis, which was in accordance with the results.Compounds 1a-l possessed excellent affinity to proteins, with binding energies ranging from −7.4 to −8.7 kcal/mol.

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Imidazopyridine chalcones as potent anticancer agents: Synthesis, single‐crystal X‐ray, docking, DFT and SAR studies

Soumyashree,

Reddy,

Nagarajaiah

et al. 2023

Archiv der Pharmazie

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New imidazopyridine–chalcone analogs were synthesized through the Claisen–Schmidt condensation reaction. The newly synthesized imidazopyridine‐chalcones (S1–S12) were characterized using spectroscopic and elemental analysis. The structures of compounds S2 and S5 were confirmed by X‐ray crystallography. The global chemical reactivity descriptor parameter was calculated using theoretically (DFT‐B3LYP‐3‐211, G) estimated highest occupied molecular orbital and lowest unoccupied molecular orbital values and the results are discussed. Compounds S1–S12 were screened on A‐549 (lung carcinoma epithelial cells) and MDA‐MB‐231 (M.D. Anderson‐Metastatic Breast 231) cancer cell lines. Compounds S6 and S12 displayed exceptional antiproliferative activity against lung A‐549 cancer cells with IC50 values of 4.22 and 6.89 µM, respectively, compared to the standard drug doxorubicin (IC50 = 3.79 μM). In the case of the MDA‐MB‐231 cell line, S1 and S6 exhibited exceptionally superior antiproliferative activity with IC50 of 5.22 and 6.50 μM, respectively, compared to doxorubicin (IC50 = 5.48 μM). S1 was found to be more active than doxorubicin. Compounds S1–S12 were tested for their cytotoxicity on human embryonic kidney 293 cells, which confirmed the nontoxic nature of the active compounds. Further molecular docking studies verified that compounds S1–S12 have a higher docking score and interacted well with the target protein. The most active compound S1 interacted well with the target protein carbonic anhydrase II in complex with pyrimidine‐based inhibitor, and S6 with human Topo IIα ATPase/AMP‐PNP. The results suggest that imidazopyridine‐chalcone analogs may serve as new leads as anticancer agents.

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Coumarin-Pyrazole Linked Carbodithioates as Potential Anti-Сancer Agents: Design, Synthesis, Biological, and Molecular Docking Investigation

Cited by 7 publications

References 57 publications

Design and Synthesis of Potent Anticancer Agents Using Coumarin‐Quinazolinone Based Scaffolds: Exploration of ADME Properties and Molecular Docking Studies

Design and Synthesis of Potent Anticancer Agents Using Coumarin‐Quinazolinone Based Scaffolds: Exploration of ADME Properties and Molecular Docking Studies

Design, synthesis, molecular docking, and biological evaluation of coumarin‐thymidine analogs as potent anti‐TB agents

Imidazopyridine chalcones as potent anticancer agents: Synthesis, single‐crystal X‐ray, docking, DFT and SAR studies

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