Design, synthesis, molecular docking, anti-proliferative and anti-TB studies of 2H-chromen-8-azaspiro[4.5]decane-7,9-dione conjugates

Mane, Smita; Reddy, D. Narasimha; Katagi, Kariyappa S.; Kumar, Amit; Munnolli, Ravindra S.; Kadam, Nikhil S.; Akki, Mahesh; Nagarajaiah, H.; Joshi, Shrinivas D.

doi:10.1016/j.molstruc.2020.129530

Cited by 9 publications

(3 citation statements)

References 21 publications

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“…Though second-and third line drugs are also available for treating TB-resistant patients, they still have some signicant disadvantages, such as long duration of treatment, higher cost involved for prolonged treatment, and poor drug compatibility. 6,7 If the most effective rst-line anti-TB drugs don't work, it leads to multidrug-resistant TB (MDR-TB), one of the most challenging origins of treating TB. As a result, the patient must move to the second-line anti-TB treatments, which combine more than ve therapies and take more than a year to work.…”

Section: Introductionmentioning

confidence: 99%

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Design, synthesis, and anti-mycobacterial evaluation of 1,8-naphthyridine-3-carbonitrile analogues

Khetmalis,

Shobha,

Nandikolla

et al. 2024

RSC Adv.

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Section: Introductionmentioning

confidence: 99%

“…This frequently leads to medication toxicity and may even cause extensively drug-resistant tuberculosis (XDR-TB). [6][7][8] There is a strong need for the development of new anti-TB medications that are more effective, take less time to work, and have higher patient compliance.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and anti-mycobacterial evaluation of 1,8-naphthyridine-3-carbonitrile analogues

Khetmalis,

Shobha,

Nandikolla

et al. 2024

RSC Adv.

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“…Recently, Apaydın et al [ 19 ] synthesize 1-thia-4-azaspiro[4.5]decane derivatives which are found potent against coronavirus. Mane et al [ 20 ] introduced novel 2 H -chromen-8-azaspiro[4.5]decane-7,9-dione conjugates and they are well inhibitors of tubercular strains and possess a significant amount of anti-proliferative activity. Amirani Poor et al [ 21 ] prepared gabapentin based spiro moieties via multicomponent Ugi reaction which active drug molecule during in silico studies.…”

Section: Introductionmentioning

confidence: 99%

Microwave produced 8-methyl-1,2,4,8-tetraazaspiro[4.5]dec-2-en-3-amine derivatives: their in vitro and in silico analysis

Patel

Tople

et al. 2023

Mol Divers

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Compound 1 is formed by a microwave-assisted multicomponent reaction of 1-methylpiperidin-4-one, 2-amino-4-methoxy-6-methyl-1,3,5-triazine, and thiosemicarbazide, followed by the synthesis of Schiff base 2a–l with a variety of aldehydes. A comparison was made between the conventional and microwave methods, and the microwave approach was shown to be considerably superior to the classical method since it takes less time and produces higher yields. Several spectral investigations, including 1 H NMR, 13 C NMR, Mass, and IR spectroscopy, are used to characterize the complete series. In vitro antibacterial testing suggests that compounds 2c , 2f , and 2g are promising antibacterial agents, although compounds 2d , 2e , and 2l are effective antimycobacterial agents when compared to the conventional medicine Rifampicin. The docking score from docking studies is considerable, which validates the results of the biological examination. Molecular docking was performed on Escherichia coli DNA gyrase . According to the in silico ADME analysis, each drug molecule is ideal for use in terms of drug solubility, hydrogen bonding, and cell permeability. Graphical abstract

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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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Design, synthesis, molecular docking, anti-proliferative and anti-TB studies of 2H-chromen-8-azaspiro[4.5]decane-7,9-dione conjugates

Cited by 9 publications

References 21 publications

Design, synthesis, and anti-mycobacterial evaluation of 1,8-naphthyridine-3-carbonitrile analogues

Design, synthesis, and anti-mycobacterial evaluation of 1,8-naphthyridine-3-carbonitrile analogues

Microwave produced 8-methyl-1,2,4,8-tetraazaspiro[4.5]dec-2-en-3-amine derivatives: their in vitro and in silico analysis

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

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