Aim: Frequent use of antibiotics is responsible for the development of antibiotic resistance; thu... more Aim: Frequent use of antibiotics is responsible for the development of antibiotic resistance; thus, there is an urgent need for the development of new antibacterial agents that act by novel mechanism pathways. Objective: The aim of the study was to develop hybrid novel 4-aminoquinoline 1,3 5-triazine derivatives and determine their antibacterial activity. Methods: Novel hybrid 4-aminoquinoline 1,3,5-triazine derivatives were synthesized by nucleophilic substitution and characterized by different spectroscopic methods. Furthermore, in silico study was carried out with 16S-rRNA A-site (PDB id: 1J7T using Discovery Studio 2018 software) to exemplify key structural interactions. In vitro antibacterial activity of target compounds was evaluated against three Gram-positive and three Gram-negative bacterial strains. Result: In silico results have shown compound 8c to have both hydrophobic interactions (conventional hydrogen bond interactions with A A:16, A A:17 and carbon hydrogen bond wit...
Journal of Biochemical and Molecular Toxicology, 2020
Parkinson's disease (PD) is a chronic neuro‐degenerative ailment characterized by impairment ... more Parkinson's disease (PD) is a chronic neuro‐degenerative ailment characterized by impairment in various motor and nonmotor functions of the body. In the past few years, adenosine A2A receptor (A2AR) antagonists have attracted much attention due to significant relief in PD. Therefore, in the current study, we intend to disclose the development of novel 1,3,5‐triazines as A2AR antagonist. The radioligand binding and selectivity of analogs were tested in HEK293 (human embryonic kidney) and the cells were transfected with pcDNA 3.1(+) containing full‐length human A2AR cDNA and pcDNA 3.1(+) containing full‐length human A1R cDNA, where they exhibit selective affinity for A2AR. Molecular docking analysis was also conducted to rationalize the probable mode of action, binding affinity, and orientation of the most potent molecule (7c) at the active site of A2AR. It has been shown that compound 7c form numerous nonbonded interactions in the active site of A2AR by interacting with Ala59, Ala63, Ile80, Val84 Glu169, Phe168, Met270, and Ile274. The study revealed 1,3,5‐triazines as a novel class of A2AR antagonists.
Journal of Biochemical and Molecular Toxicology, 2021
The present manuscript deals with the development of novel p‐aminobenzoic acid (PABA) associated ... more The present manuscript deals with the development of novel p‐aminobenzoic acid (PABA) associated 1,3,5‐triazine derivatives as antimalarial agents. The molecules were developed via microwave‐assisted synthesis and structures of compounds were ascertained via numerous analytical and spectroscopic techniques. The synthesized compounds were also subjected to ADMET analysis. In a docking analysis, the title compounds showed high and diverse binding affinities towards wild (−162.45 to −369.38 kcal/mol) and quadruple mutant (−165.36 to −209.47 kcal/mol) Pf‐DHFR‐TS via interacting with Phe58, Arg59, Ser111, Ile112, Phe116. The in vitro antimalarial activity suggested that compounds 4e, 4b, and 4h showed IC50 ranging from 4.18 to 8.66 μg/ml against the chloroquine‐sensitive (3D7) strain of Plasmodium falciparum. Moreover, compounds 4g, 4b, 4e, and 4c showed IC50 ranging from 8.12 to 12.09 μg/ml against chloroquine‐resistant (Dd2) strain. In conclusion, our study demonstrated the development of hybrid PABA substituted 1,3,5‐triazines as a novel class of Pf‐DHFR inhibitor for antimalarial drug discovery.
1,3,5‐Triazine and its derivatives have been the epicenter of chemotherapeutic molecules due to t... more 1,3,5‐Triazine and its derivatives have been the epicenter of chemotherapeutic molecules due to their effective biological activities, such as antibacterial, fungicidal, antimalarial, anticancer, antiviral, antimicrobial, anti‐inflammatory, antiamoebic, and antitubercular activities. The present review represents a summarized report of the crucial biological activities possessed by substituted 1,3,5‐triazine derivatives, with special attention to the most potent compounds.
A series of substituted phenylthiazolyl 1,3,5-triazine derivatives were screened for their in-vit... more A series of substituted phenylthiazolyl 1,3,5-triazine derivatives were screened for their in-vitro antifungal activity (MIC and MFC) against four fungi viz. Candida species (C. albicans NCIM-3102, C. glabrata NCIM-3266), Cryptococcus neoformans NCIM-3542, and Aspergillus niger NCIM-620 using modified broth microdilution method recommended by CLSI, with reference to fluconazole and amphotericin B.
The heterocyclic compounds include a vast subject in chemistry and thiazole is one of the leading... more The heterocyclic compounds include a vast subject in chemistry and thiazole is one of the leading heterocyclic compounds which have a five-member ring with the molecular formula C3H3NS containing sulphur and nitrogen atoms, occupies an important place in pharmaceutical chemistry. Many natural and synthetic medicinally important compounds contain thiazole as essential moieties with a broad range of therapeutic activities. Diverse modifications of the thiazole ring at various positions led to a variety of novel compounds with a wide spectrum of pharmacological activities such as antibacterial, antioxidant, diuretic, antifungal, antitubercular, anti-inflammatory, anticonvulsant, anti-HIV, antidiabetic, antihypertensive, anti-Alzheimer and anticancer activities. Research has been carried out with an aim to discover the therapeutic values of thiazole moiety and a number of these compounds became famous in the antibacterial market due to their therapeutic efficacy which has great pharmace...
A novel series of hybrid analogues of monastrol-1,3,5-triazine were designed and developed via on... more A novel series of hybrid analogues of monastrol-1,3,5-triazine were designed and developed via one-pot synthesis using Bi(NO3)3 as a catalyst. Entire compounds were evaluated for their anticancer activity against HeLa (cervical cancer), MCF-7 (breast cancer), HL-60 (Human promyelocytic leukemia), HepG2 (Hepatocellular carcinoma) and MCF 12A (normal epithelial breast cell line) using MTT assay, where they showed highest inhibitory activity against MCF-7. The molecules were also found to be non-toxic to MCF 12A cells. These molecules showed considerable inhibitory percentage against Epidermal Growth Factor Receptor tyrosine kinase (EGFR-TK), in in-vitro assay. Molecular docking study was carried out on the analogs and reference compound (Erlotinib) into the ATP binding site of EGFR-TK domain (PDB ID:1M17) to elucidate vital structural residues necessary for bioactivity. The effect of most active compound 7l was also estimated in-vivo in DMBA induced mammary tumor in female Sprague-Daw...
A series of hybrid thiazolidin-4-one-1,3,5-triazines was evaluated for NF-κB, biofilm and CFTR ac... more A series of hybrid thiazolidin-4-one-1,3,5-triazines was evaluated for NF-κB, biofilm and CFTR activity.
Aim: Frequent use of antibiotics is responsible for the development of antibiotic resistance; thu... more Aim: Frequent use of antibiotics is responsible for the development of antibiotic resistance; thus, there is an urgent need for the development of new antibacterial agents that act by novel mechanism pathways. Objective: The aim of the study was to develop hybrid novel 4-aminoquinoline 1,3 5-triazine derivatives and determine their antibacterial activity. Methods: Novel hybrid 4-aminoquinoline 1,3,5-triazine derivatives were synthesized by nucleophilic substitution and characterized by different spectroscopic methods. Furthermore, in silico study was carried out with 16S-rRNA A-site (PDB id: 1J7T using Discovery Studio 2018 software) to exemplify key structural interactions. In vitro antibacterial activity of target compounds was evaluated against three Gram-positive and three Gram-negative bacterial strains. Result: In silico results have shown compound 8c to have both hydrophobic interactions (conventional hydrogen bond interactions with A A:16, A A:17 and carbon hydrogen bond wit...
Journal of Biochemical and Molecular Toxicology, 2020
Parkinson's disease (PD) is a chronic neuro‐degenerative ailment characterized by impairment ... more Parkinson's disease (PD) is a chronic neuro‐degenerative ailment characterized by impairment in various motor and nonmotor functions of the body. In the past few years, adenosine A2A receptor (A2AR) antagonists have attracted much attention due to significant relief in PD. Therefore, in the current study, we intend to disclose the development of novel 1,3,5‐triazines as A2AR antagonist. The radioligand binding and selectivity of analogs were tested in HEK293 (human embryonic kidney) and the cells were transfected with pcDNA 3.1(+) containing full‐length human A2AR cDNA and pcDNA 3.1(+) containing full‐length human A1R cDNA, where they exhibit selective affinity for A2AR. Molecular docking analysis was also conducted to rationalize the probable mode of action, binding affinity, and orientation of the most potent molecule (7c) at the active site of A2AR. It has been shown that compound 7c form numerous nonbonded interactions in the active site of A2AR by interacting with Ala59, Ala63, Ile80, Val84 Glu169, Phe168, Met270, and Ile274. The study revealed 1,3,5‐triazines as a novel class of A2AR antagonists.
Journal of Biochemical and Molecular Toxicology, 2021
The present manuscript deals with the development of novel p‐aminobenzoic acid (PABA) associated ... more The present manuscript deals with the development of novel p‐aminobenzoic acid (PABA) associated 1,3,5‐triazine derivatives as antimalarial agents. The molecules were developed via microwave‐assisted synthesis and structures of compounds were ascertained via numerous analytical and spectroscopic techniques. The synthesized compounds were also subjected to ADMET analysis. In a docking analysis, the title compounds showed high and diverse binding affinities towards wild (−162.45 to −369.38 kcal/mol) and quadruple mutant (−165.36 to −209.47 kcal/mol) Pf‐DHFR‐TS via interacting with Phe58, Arg59, Ser111, Ile112, Phe116. The in vitro antimalarial activity suggested that compounds 4e, 4b, and 4h showed IC50 ranging from 4.18 to 8.66 μg/ml against the chloroquine‐sensitive (3D7) strain of Plasmodium falciparum. Moreover, compounds 4g, 4b, 4e, and 4c showed IC50 ranging from 8.12 to 12.09 μg/ml against chloroquine‐resistant (Dd2) strain. In conclusion, our study demonstrated the development of hybrid PABA substituted 1,3,5‐triazines as a novel class of Pf‐DHFR inhibitor for antimalarial drug discovery.
1,3,5‐Triazine and its derivatives have been the epicenter of chemotherapeutic molecules due to t... more 1,3,5‐Triazine and its derivatives have been the epicenter of chemotherapeutic molecules due to their effective biological activities, such as antibacterial, fungicidal, antimalarial, anticancer, antiviral, antimicrobial, anti‐inflammatory, antiamoebic, and antitubercular activities. The present review represents a summarized report of the crucial biological activities possessed by substituted 1,3,5‐triazine derivatives, with special attention to the most potent compounds.
A series of substituted phenylthiazolyl 1,3,5-triazine derivatives were screened for their in-vit... more A series of substituted phenylthiazolyl 1,3,5-triazine derivatives were screened for their in-vitro antifungal activity (MIC and MFC) against four fungi viz. Candida species (C. albicans NCIM-3102, C. glabrata NCIM-3266), Cryptococcus neoformans NCIM-3542, and Aspergillus niger NCIM-620 using modified broth microdilution method recommended by CLSI, with reference to fluconazole and amphotericin B.
The heterocyclic compounds include a vast subject in chemistry and thiazole is one of the leading... more The heterocyclic compounds include a vast subject in chemistry and thiazole is one of the leading heterocyclic compounds which have a five-member ring with the molecular formula C3H3NS containing sulphur and nitrogen atoms, occupies an important place in pharmaceutical chemistry. Many natural and synthetic medicinally important compounds contain thiazole as essential moieties with a broad range of therapeutic activities. Diverse modifications of the thiazole ring at various positions led to a variety of novel compounds with a wide spectrum of pharmacological activities such as antibacterial, antioxidant, diuretic, antifungal, antitubercular, anti-inflammatory, anticonvulsant, anti-HIV, antidiabetic, antihypertensive, anti-Alzheimer and anticancer activities. Research has been carried out with an aim to discover the therapeutic values of thiazole moiety and a number of these compounds became famous in the antibacterial market due to their therapeutic efficacy which has great pharmace...
A novel series of hybrid analogues of monastrol-1,3,5-triazine were designed and developed via on... more A novel series of hybrid analogues of monastrol-1,3,5-triazine were designed and developed via one-pot synthesis using Bi(NO3)3 as a catalyst. Entire compounds were evaluated for their anticancer activity against HeLa (cervical cancer), MCF-7 (breast cancer), HL-60 (Human promyelocytic leukemia), HepG2 (Hepatocellular carcinoma) and MCF 12A (normal epithelial breast cell line) using MTT assay, where they showed highest inhibitory activity against MCF-7. The molecules were also found to be non-toxic to MCF 12A cells. These molecules showed considerable inhibitory percentage against Epidermal Growth Factor Receptor tyrosine kinase (EGFR-TK), in in-vitro assay. Molecular docking study was carried out on the analogs and reference compound (Erlotinib) into the ATP binding site of EGFR-TK domain (PDB ID:1M17) to elucidate vital structural residues necessary for bioactivity. The effect of most active compound 7l was also estimated in-vivo in DMBA induced mammary tumor in female Sprague-Daw...
A series of hybrid thiazolidin-4-one-1,3,5-triazines was evaluated for NF-κB, biofilm and CFTR ac... more A series of hybrid thiazolidin-4-one-1,3,5-triazines was evaluated for NF-κB, biofilm and CFTR activity.
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