Synthesis, and biological screening of chloropyrazine conjugated benzothiazepine derivatives as potential antimicrobial, antitubercular and cytotoxic agents

Shaik, Afzal B.; Bhandare, Richie R.; Nissankararao, Srinath; Lokesh, Bontha Venkata Subrahmanya; Shahanaaz, Shaik; Rahman, Md. Abdur

doi:10.1016/j.arabjc.2020.102915

Cited by 18 publications

(12 citation statements)

References 55 publications

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“…The in vitro antiproliferative activity of pyrimidine derivatives (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) was screened against DU-145 (prostate cancer cell lines) by the renowned Mosmann's MTT (3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay method [54]. The antiproliferative activity of 22-40 was measured to determine their IC 50 values by comparison against reference standard Methotrexate (Mtx; positive control).…”

Section: Antiproliferative Activitymentioning

confidence: 99%

“…Similarly, pyrimidine-based compounds also showed excellent antimicrobial (antibacterial and antifungal) [29][30][31][32][33], antimycobacterial [34][35][36][37][38], antioxidant [39][40][41][42], cytotoxic and anticancer [42][43][44][45][46][47][48][49][50][51][52], and antiviral [51][52][53] properties. In our previous study, we reported the antimicrobial and antiproliferative activities of chloropyrazine-linked 1,5-benzothiazepine hybrids [54]. Considering the significant biological activities of pyrimidine derivatives, previously we synthesized and evaluated the antitubercular activity of chloropyrazine-tethered pyrimidine hybrids (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)…”

Section: Introductionmentioning

confidence: 99%

“…Here, we report the antimicrobial as well as the antiproliferative activities of chloropyrazine-tethered pyrimidine hybrids with the aim to develop potent antimicrobial and antiproliferative hybrids. In our previous study, we reported the antimicrobial and antiproliferative activities of chloropyrazine-linked 1,5-benzothiazepine hybrids [54]. Considering the significant biological activities of pyrimidine derivatives, previously we synthesized and evaluated the antitubercular activity of chloropyrazine-tethered pyrimidine hybrids (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) [55].…”

Section: Introductionmentioning

confidence: 99%

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Assessment of the Antimicrobial and Antiproliferative Activities of Chloropyrazine-Tethered Pyrimidine Derivatives: In Vitro, Molecular Docking, and In-Silico Drug-Likeness Studies

Bhandare

Shaik

2021

Applied Sciences

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Molecular hybridization (MH) of heterocyclic rings has enabled scientists to design and develop novel drugs and drug-like candidates. In our previous work, considering the importance of MH, we synthesized different kinds of chloropyrazine-tethered pyrimidine derivatives (22–40) containing either substituted phenyl or heteroaryl rings at position-6 of the pyrimidine ring and evaluated their antitubercular activity. Herein, we report the antimicrobial and antiproliferative activities of 22–40. The antiproliferative activity of the target hybrids was superior to the antimicrobial activity. However, some compounds showed greater antimicrobial activity than the standard drugs. For instance, among the nineteen derivatives, compound 31 containing a 2″,4″-dichlorophenyl ring, showed the most potent antibacterial and antifungal activities (MIC 45.37 µM), followed by compounds 25 and 30 bearing 4″-nitrophenyl and 2″,4″-difluorophenyl scaffolds with minimum inhibitory concentrations (MIC) values of 48.67 µM and 50.04 µM, respectively. Compound 35, containing a bioisosteric 2″-pyridinyl ring, showed the most potent antiproliferative activity against the prostate cancer cell line (DU-145) with an IC50 value of 5 ± 1 µg/mL. Additional testing of compounds 22–40 on human normal liver cells (LO2) indicated that the compounds were more selective to cancer cell lines over normal cells. Further, molecular docking of the most potent compound 35 against dihydrofolate reductase (DHFR) (PDB ID: 1U72) had a good binding affinity with a docking score of −6.834. The SwissADME program estimated the drug-likeness properties of compound 35. Hybrid 35 is a potential lead molecule for the development of new anticancer drugs, whereas 31 is a promising antimicrobial lead candidate.

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Section: Antiproliferative Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Assessment of the Antimicrobial and Antiproliferative Activities of Chloropyrazine-Tethered Pyrimidine Derivatives: In Vitro, Molecular Docking, and In-Silico Drug-Likeness Studies

Bhandare

Shaik

2021

Applied Sciences

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“…Similar to homocyclic benzoheterodiazepine, green, economical, and eco-friendly reaction condition is significant in drug design [163]. For instance, 1,5-benzodiazepine (53) has been prepared using polyethylene glycol (PEG-400) as a solvent for inexpensive, non-toxic, potentially recyclable, non-halogenated, and water-soluble media to facilitate the removal of the reaction product.…”

Section: S C H E M E 1 1 Synthesis Of Heterocyclic Benzodiazepine Compoundsmentioning

confidence: 99%

Chalcone derived benzoheterodiazepines for medicinal applications: A Two‐pot and one‐pot synthetic approach

Farooq

Ngaini

2021

Journal of Heterocyclic Chem

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“…The IC 50 was determined as the concentration that decreased the absorbance of the untreated wells by 50% relative to vehicle in the MTT test. Triplicate assays were conducted and the reproducibility of the findings was excellent with standard errors below 10% [24,25].…”

Section: Cytotoxicity Studiesmentioning

confidence: 99%

Isoxazole Clubbed 1-carbothioamido-4,5-dihydro-1H-pyrazoles: Design, Synthesis, Characterization and Antitubercular Evaluation

Gopal

Murthy²

2021

JPRI

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Tuberculosis (TB) is a global problem inspite the availability of drugs. This state of affairs is due to the limitations of existing drugs including muti-drug resistance and toxicites. As a result, there is a pressing need for new antitubercular medicines to be developed. In the present investigation we designed and synthesized a series of isoxazole clubbed 1-carbothioamido-4,5-dihydro-1H-pyrazoles (16-30) in considerable yeilds (43-78%). Further these compounds were purified by recrystallization and charcterized by spectral techniques-Mass, FT-IR and 1H NMR and then evaluated for their antitubercular activity against Mycobacterium tuberculosis H37Rv strain. Among the tested compounds, the analogues 24 bearing 3,5-dimethoxyphenyl scaffold at the 5th position of 4,5-dihydro-1H-pyrazole ring showed superior activity than isoniazid (MIC = 0.25 µg/mL) with MIC value 0.1 µg/mL whereas the compound 25 containing 2,3,4-trimethoxyphenyl had equal potency as that of isoniazid. Additionally, 24 and 25 were found to be less selective towards the human normal liver cell lines-LO2 in their cytotoxicity assays. Hence, these two compounds are safe and useful lead candidates for the development of novel antitubercular drugs.

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Synthesis, and biological screening of chloropyrazine conjugated benzothiazepine derivatives as potential antimicrobial, antitubercular and cytotoxic agents

Cited by 18 publications

References 55 publications

Assessment of the Antimicrobial and Antiproliferative Activities of Chloropyrazine-Tethered Pyrimidine Derivatives: In Vitro, Molecular Docking, and In-Silico Drug-Likeness Studies

Assessment of the Antimicrobial and Antiproliferative Activities of Chloropyrazine-Tethered Pyrimidine Derivatives: In Vitro, Molecular Docking, and In-Silico Drug-Likeness Studies

Chalcone derived benzoheterodiazepines for medicinal applications: A Two‐pot and one‐pot synthetic approach

Isoxazole Clubbed 1-carbothioamido-4,5-dihydro-1H-pyrazoles: Design, Synthesis, Characterization and Antitubercular Evaluation

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