Synthesis and pharmacological evaluation of 1,3,4-thiadiazole bearing pyrimidine derivatives as STAT3 inhibitor for treatment of breast cancer

Sravanthi, Bommagani; Lakshmanan, Kaviarasan; Krishnamurthy, Praveen Thaggikuppe; Pindiprolu, Sai Kiran S. S.; Pavankumar, C.; Byran, Gowramma

doi:10.1007/s13738-020-01932-z

Cited by 6 publications

(3 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The synthesis of nitrogen and sulphur containing fused heterocyclic compounds with multi-structures in one molecule has attracted the attention of medicinal chemists and researchers due to their multifaceted pharmacological activities [1][2]. Among them, pyrimidine and thiophene have been recognized as key scaffolds owing to their important biological significances and interesting therapeutic properties including anti-tubercular [3], anticancer [4], anti-HIV [5], antibacterial [6], antifungal [7], antitumor [8], also used as potent EGFR inhibitor [9, 10], protein kinase inhibitors [11][12][13][14] and 5-HT7 receptors [15].…”

Section: Introductionmentioning

confidence: 99%

Facile synthesis of some 5-(3-substituted-thiophene)-pyrimidine derivatives and their pharmacological and computational studies

et al. 2021

View full text Add to dashboard Cite

A series of 5-(3-substituted-thiophene)-pyrimidine derivatives (3a-d) were synthesized via Knoevenagel condensation reaction in aq. ethanol using H2O2:HCl as a catalyst. Their pharmacological effects were evaluated. Analytical and spectroscopic methods confirmed the structures of the target molecules. The antibacterial activity studies revealed that compounds 3b and 3d exhibited the most effective zone of inhibition against bacterial strains E. coli and S. aureus, respectively. The in vitro cytotoxicity was carried out by MTT assay against MCF-7 cell line. The results showed excellent selectivity for all four compounds, among which the compound 3a exhibited remarkable cytotoxicity with a minimum cell viability range of 23.68 to 44.16%. The interaction of compounds with calf thymus DNA was determined using UV-absorption spectroscopy. The results confirmed that all the synthesized compounds interacted strongly with CT DNA through electrostatic or groove binding. In silico ADME-toxicology studies indicated that all the molecules under investigation are non-toxic with good oral bioavailability. The drug-likeness score indicated that they are suitable as drug-leads. In silico molecular docking the specified compound 3b bound with GlcN-6-P and P38 MAPk with a minimum binding energy of –7.9 and –6.4 kcal/mol, respectively. DFT study demonstrated that compound 3d was chemically and biologically more reactive due to less energy gap.

show abstract

Section: Introductionmentioning

confidence: 99%

Facile synthesis of some 5-(3-substituted-thiophene)-pyrimidine derivatives and their pharmacological and computational studies

et al. 2021

View full text Add to dashboard Cite

show abstract

“…A series of 6-cyano-1,3,4-thidiazolo-[3,2-a]pyrimidine derivatives was synthesized [16], they showed good binding mode in the active site of STAT3 enzyme inhibitors [17] and to treat breast cancer [18]. The cytotoxic activity [19] was found in 2-alkanesul nyl/alkanesulfonyl-7-methyl-5H-1,3,4-thiadiazolo [3,2α]pyrimidin-5-one derivatives [20], especially the strong activity was shown by the compounds which have electrophilic substituent group on the 2-position such as alkyl sulfoxide or alkyl sulfone.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Screening of New Thiadiazolopyrimidine-based Polycyclic Compounds

Alqahtani

2021

Preprint

View full text Add to dashboard Cite

New tri- and tetra-cyclic compounds based on the thiadiazolopyrimidine ring system were prepared and their antimicrobial activity were estimated. The achieved results evidenced that pyrano-thiadiazolopyrimidine compounds 8a-b and 9a-b have substantial efficiencies toward the two strains of Gram-positive bacteria (S. aureus and B. cereus). While tetracyclic derivatives pyrazolopyrimido-thiadiazolopyrimidine derivatives 16a-b and 17a-b displayed prominent efficiencies toward the two strains of Gram-negative bacteria (E. coli and P. aeruginosa). In addition, compounds 8a-b and 9a-b presented good efficacy toward C. albicans. The activity of antiquorum-sensing (anti-QS) inhibition of the new synthesized thiadiazolopyrimidine-based compounds was tested toward C. violaceum, where derivatives 16a-b, 17a-b, 8b and 9a displayed satisfactory activity. Cytotoxic activity of the same derivatives was screened toward various cancer cell lines (MCF-7, PC3, Hep-2 and HepG2) and standard normal fibroblast cell (WI38) by utilizing the MTT assay. The pyrazolopyrimido-thiadiazolopyrimidine derivatives 16a, 16b, 17a and 17b recorded potent cytotoxic efficacy against MCF-7 cells with IC50 values ranging from 5.69 to 9.36 µM. Also, the endorsed structural activity relationship (SAR) for the inspected thiadiazolopyrimidine derivatives provided an awareness concerning the chemical structure connected to anticancer efficiency. In silico docking studies were implemented toward silence hormone signaling in breast (PDB Code-5NQR). The results are consistent and supportive to the cytotoxic activity.

show abstract

“…A series of 6-cyano-1,3,4-thiadiazolo[3,2- a ]pyrimidine derivatives 16 showing a good binding mode in the active site of STAT3 enzyme inhibitors 17 was synthesized to treat breast cancer 18 . The 2-alkanesulfinyl/alkanesulfonyl-7-methyl-5 H -1,3,4-thiadiazolo[3,2-α]pyrimidin-5-one derivatives 19 showed good cytotoxic activity 20 , with exceptionally strong activity for the compounds containing electrophilic substituents, such as alkyl sulfoxide or alkyl sulfone, on the 2-position.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biological screening of new thiadiazolopyrimidine-based polycyclic compounds

Alqahtani

2021

Sci Rep

View full text Add to dashboard Cite

Novel tri-and tetra-cyclic compounds based on the thiadiazolopyrimidine ring system were synthesized, and their antimicrobial activity was estimated. The obtained results evidenced the substantial efficiencies of pyrano-thiadiazolopyrimidine compounds 8a–b and 9a–b toward the two strains of gram-positive bacteria (S. aureus and B. cereus). Besides, tetracyclic pyrazolopyrimido-thiadiazolopyrimidine derivatives 16a–b and 17a–b displayed prominent efficiencies toward the two strains of gram-negative bacteria (E. coli and P. aeruginosa). In addition, compounds 8a–b and 9a–b displayed good efficacy toward C. albicans. The activity of antiquorum sensing (anti-QS) inhibition of the newly synthesized thiadiazolopyrimidine-based compounds toward C. violaceum was tested, suggesting satisfactory activity for derivatives 16a–b, 17a–b, 8b, and 9a. The cytotoxic activity of these derivatives was screened toward various cancer cell lines (MCF-7, PC3, Hep-2, and HepG2) and standard normal fibroblast cells (WI38) by utilizing the MTT assay. The pyrazolopyrimido-thiadiazolopyrimidine derivatives 16a, 16b17a, and 17b showed potent cytotoxic efficacy against the MCF-7 cells with the IC50 values ranging from 5.69 to 9.36 µM. Also, the endorsed structural activity relationship (SAR) of the inspected thiadiazolopyrimidine derivatives provided a correlation between the chemical structure and anticancer efficiency. The in silico docking studies were implemented for silencing the hormonal signaling in the breast (PDB Code-5NQR). The results were found to be consistent with the cytotoxic activity.

show abstract

Synthesis and pharmacological evaluation of 1,3,4-thiadiazole bearing pyrimidine derivatives as STAT3 inhibitor for treatment of breast cancer

Cited by 6 publications

References 17 publications

Facile synthesis of some 5-(3-substituted-thiophene)-pyrimidine derivatives and their pharmacological and computational studies

Facile synthesis of some 5-(3-substituted-thiophene)-pyrimidine derivatives and their pharmacological and computational studies

Synthesis and Biological Screening of New Thiadiazolopyrimidine-based Polycyclic Compounds

Synthesis and biological screening of new thiadiazolopyrimidine-based polycyclic compounds

Contact Info

Product

Resources

About