Sirassu Narsimha

Indole-2-carboxylic acid derived mono and bis 1,4-disubstituted 1,2,3-triazoles: Synthesis, characterization and evaluation of anticancer, antibacterial, and DNA-cleavage activities

A series of new indole-2-carboxylic acid derived mono and bis 1,4-disubstituted 1,2,3 triazoles (I(1)-I(6) and I(7)-I(12)) were synthesized and screened for their anticancer (in vitro and in vivo), antibacterial, and DNA cleavage activities. All the synthesized compounds were characterized by spectral studies. The in vitro anticancer screening results revealed that compound I(12) has registered potential activity against MCF-7, HeLa and HEK293 as compared with the standard reference drug Cisplatin. Remaining compounds have exhibited moderate to good activity against three cancer cell lines. The antibacterial activity screening results revealed that compounds, I(6) and I(12) have registered excellent inhibition against Escherichia coli and Bacillus subtilis in comparison with the standard drug Streptomycin. Compounds I(2) and I(11) have partially cleaved the DNA at 100 μg mL(-1) concentration.

Synthesis and antibacterial activity of (1-aryl-1, 2, 3-triazol-4-yl) methyl esters of morpholine-3-carboxylic acid

A series of new 1,2,3-triazolyl methyl ester of morpholine-3-carboxylic acid analogues were designed and synthesized employing click chemistry by using Huisgen 1,3 dipolar cyclo addition reaction between propargyl ester of morpholine-3-carboxylic acid and aryl azides. The starting materials propargyl ester and aryl azides were synthesized by well established methods. The newly synthesized compounds were characterized by spectral studies. The compounds were screened for antibacterial activity. Majority of the compounds exhibited promising activity and one of them (6i) displayed more activity than standard drug against S. paratyphi-B. A molecular docking study showed hydrogen bonds and pi-interactions with the compound. Our data indicate that these derivatives may present promising anti-bacterial agents.Graphical Abstract

Novel substituted hydrazono indolo[2,1-b]quinazoline-6,12-dione analogues as cytostatic agents: Synthesis, crystal structure, biological evaluation and molecular docking studies.

A series of novel substituted hydrazono indolo[2,1-b]quinazoline-6,12-dione analogues have been synthesized and screened for their in vitro cytotoxic and antimicrobial activities. Among all the target compounds, 3c exhibited the most potent inhibitory activity against three cancer cell lines MCF-7, A549, HeLa with IC50 values 07.14±1.285μM, 09.18±0.968μM and 10.57±0.581μM respectively, while maintaining low toxicity towards non-cancer originated cell line, HEK-293. The detailed studies about molecular interactions with probable target protein indoleamine 2,3-dioxygenase (IDO1) were done by using docking simulations. The results from docking models are in consistent with the experimental in vitro cytotoxic activity conclusions i.e. 3c shows the highest binding energy -11.25kcal/mol. Furthermore, antimicrobial studies revealed that the compound 3e has shown excellent anti bacterial activity against four tested strains and the compounds 3b, 3e and 3f have shown good anti fungal activity against two tested organisms as compared with their standard drugs.

N,N′-(hexane-1,6-diyl)bis(N-((1-aryl/alkyl-1H-1,2,3-triazol-4-yl)methyl)-4-methyl benzenesulfonamide): Synthesis, antibacterial, antioxidant, and DNA-cleavage activities

GRAPHICAL ABSTRACT ABSTRACT Thirteen novel bis-1,2,3-triazole derivatives were synthesized under copper (I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition of N,N′-(hexane-1,6-diyl)bis(4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide) with different aryl azides and evaluated their biological activity. All the newly synthesized compounds were confirmed by 1H-NMR, infrared, and elemental analysis and mass spectral studies. The synthesized bis-1,2,3-triazoles were evaluated for their antioxidant activity, and some of them were found to exhibit good to excellent antioxidant activity (IC50: 11.13 ± 1.5 to 98.98 ± 1.7 μM) in comparison with standard references, Trolox (11.73 ± 1.5 μM) and ascorbic acid (3.34 ± 1.8 μM). The bistriazoles also exhibited excellent-to-moderate anti-bacterial activity (MIC: 2.253 to 75 µg mL−1 against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa when compared with streptomycin. N,N′-(hexane-1,6-diyl)bis(N-((1-(3,5-dimethylphenyl)-1H-1,2,3-triazol-4-yl)methyl)-4-methyl benzenesulfonamide) has completely cleaved the DNA at a concentration of 100 mg mL−1, and the remaining compounds have partially cleaved the DNA.

One-pot synthesis of fused benzoxazino[1,2,3]triazolyl[4,5-c]quinolinone derivatives and their anticancer activity

A one pot strategy for the synthesis of fused benzoxazino[1,2,3]triazolyl[4,5-c]quinolinone derivatives 4a–4k via the reaction of 5-iodo-4-(prop-2-yn-1-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (3) with different aryl azides under copper and palladium catalysis in a ligand free condition is achieved. The reaction provided the desired fused triazoles in good to excellent yields. The synthesized derivatives were evaluated for their in vitro cytotoxic activity against MCF-7, A-549 and HeLa cancer cell lines using MTT assay. The cytotoxic activity results revealed that, compound 4d has shown a broad spectrum of activity against MCF-7 and A-549 with IC50 values of 11.18 ± 0.8 and 17.81 ± 0.6 μM, which are comparable to the standard drug, cisplatin. The remaining compounds have shown good to moderate activity against the tested cell lines. Based on the results obtained, a structure activity relationship (SAR) is discussed.

Design, synthesis, and biological evaluation of novel substituted imidazo[2,1-a]isoindole derivatives as antibacterial agents

ABSTRACT An efficient protocol has been developed for the synthesis of fused imidazo[2,1-a]isoindol-5-ones (2a–d) from 2-iodo benzoic acids and N,N-carbonyldiimidazole (CDI) using one-pot Pd-catalyzed C‒C bond coupling. The reaction of imidazo[2,1-a]isoindol-5-one (2a–d) with substituted α-bromo ketones in toluene afforded corresponding imidazo[2,1-a]isoindolium derivatives (3a–i) in good yields. The structures of the title compounds were well established on the basis of infrared (IR), 1H NMR, carbon-13 nuclear magnetic resonance (13C NMR), mass spectral data, and elemental analysis (C, H, and N). In vitro antibacterial results revealed that, the compounds 3b and 3i were found to possess an excellent broad spectrum of inhibiting potency against all the tested bacterial strains with minimum inhibitory concentration values ranging from 3.125 to 25 µg mL−1. GRAPHICAL ABSTRACT

Synthesis, characterization and biological evaluation of 7-substituted-4-((1-aryl-1H-1,2,3-triazol-4-yl) methyl)-2H-benzo[b][1,4]oxazin-3(4H)-ones as anticancer agents

A series of novel 1,2,3-triazole-2H-benzo[b][1,4]oxazin-3(4H)-ones (4a–4k and 5a–5g) were designed, synthesized and screened for their anticancer activity against MCF-7 (breast) and HeLa (cervical) cell lines using [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] assay. Among all the tested compounds, 5b and 5c exhibited good cytotoxic activity against two cancer cell lines with IC50 values nearer to the standard drug, cisplatin. The most active compounds 5b and 5c were further evaluated for their in vivo anticancer activity against Ehrlich Ascites Carcinoma-bearing mice and compound 5c found to possess potential cytotoxic activity as compared with the reference drug cisplatin. Molecular docking studies were also carried out to complement the experimental results.

One-pot synthesis of novel 1,2,3-triazole-pyrimido[4,5-c]isoquinoline hybrids and evaluation of their antioxidant activity

ABSTRACT A series of novel pyrimido[4,5-c]isoquinolines (3a–3h) and 1,2,3-triazole-coupled pyrimido[4,5-c]isoquinolines (4a–4h) were synthesized in good to excellent yields in the one-pot method. The reaction of 6-amino-1,3-dimethyluracil with different 2-iodo benzoyl chlorides using Pd catalyst in dimethylformamide afforded corresponding pyrimido[4,5-c]isoquinolines (3a–3h). One-pot reaction of pyrimido[4,5-c]isoquinolines with propargyl bromide and benzyl azide in THF at room temperature furnished 1,2,3-triazole-coupled pyrimido[4,5-c]isoquinoline (4a–4h). In vitro antioxidant activity examination revealed that compounds 4d and 4c found to exhibit potent antioxidant activity as compared to the standard drug Trolox with IC50 values 6.02 ± 0.6 and 12.18 ± 0.9 µM, respectively. GRAPHICAL ABSTRACT