Suhas A. Shintre

Synthesis and anti-bacterial evaluation of novel thio- and oxazepino[7,6-b]quinolines

AbstractCyclocondensation of 2-chloroquinoline-3-carbaldehydes and 2-thiophenol/2-aminophenols led to the formation of benzo[2,3][1,4]thio- or oxazepino[7,6-b]quinolines. Ugi reaction of the latter compound with various carboxylic acids and isocyanides gave novel oxazepino[7,6-b]quinoline derivatives. All compounds were evaluated for their anti-bacterial and anti-fungal activities. Among them, compounds 4a, 4b and 4d showed moderate to good activity.

Molecular diversity in cyclization of Ugi-products leading to the synthesis of 2,5-diketopiperazines: computational study

Ugi-adducts were obtained via a one-pot four-component reaction of divergent aldehydes, amines, aroylacrylic acids and isocyanide in methanol. These products were subjected to intramolecular Michael addition in the presence of K2CO3 in DMF at room temperature to afford a single product. Literally, the formation of two heterocyclic systems, 6-membered diones or 7-membered diones are possible, which could not be identified by conventional spectroscopic methods. The X-ray crystallographical data was obtained for one selected product, which indicated preferential formation of the corresponding 6-membered dione. In order to establish the generality of this mode of cyclization, the quantum chemistry calculations were performed. The obtained results confirmed the favorable formation of 6-membered diones in the gas and also several solution phases. All the products were screened for their antibacterial and antifungal activities.Graphical Abstract

Transition metal-free synthesis of quinolino[2′,3′:3,4]pyrazolo[5,1-b]quinazolin-8(6H)-ones via cascade dehydrogenation and intramolecular N-arylation

Abstract2-(2-Chloroquinolin-3-yl)-3-(arylamino)-2,3-dihydroquinazolin-4(1H)-one was converted to quinolino[2′,3′:3,4]pyrazolo[5,1-b]quinazolin-8(6H)-ones in the presence of KOtBu in DMSO at room temperature. The present method has the advantages of easy conditions, construction of highly novel five heterocycles, transition metal-free conditions, cascade dehydrogenation and intramolecular N-arylation and good to high yield of products.

Synthesis, in vitro antimicrobial, antioxidant, and antidiabetic activities of thiazolidine–quinoxaline derivatives with amino acid side chains

A novel protocol for the rapid assembly of a hybrid framework based on amino acid, thiazolidine and quinoxaline scaffolds has been demonstrated by microwave irradiation. The quinoxalines with amino acid side chains 5a–5c were prepared in three steps from 2,4-dinitrofluorobenzene and the amino acids, valine, methionine, and tyrosine and subsequently reacted with four different aldehydes and thioglycolic acid to produce thiazolidine–quinoxaline hybrids with amino acid side chains 6a–6l. All synthesized compounds were evaluated for their in vitro antimicrobial, antioxidant, and antidiabetic activities. Compounds 6f, 6j, and 6k showed broad spectrum antimicrobial activity against Gram +ve and Gram –ve bacteria, whilst 6h, 6k, and 6l showed the best antioxidant activity in the same order of magnitude to that of ascorbic acid. Four of the compounds, 5c, 6d, 6g, and 6k showed activity against α-glucosidase and α-amylase similar to acarbose. Those compounds showing antibacterial activity possessed 4-fluorophenyl and 4-methoxyphenyl groups along with methionine and tyrosine side chains while the compounds showing antioxidant, α-glucosidase, and α-amylase activity contained 4-nitrophenyl and 4-methoxyphenyl groups on the thiazolidine moiety with mainly methionine and tyrosine side chains. The α-glucosidase and α-amylase inhibitory compound 5c did not have a thiazolidine moiety and 6d was the only active compound with a valine amino acid side chain. Compound 6k with a tyrosine side chain and a 4-methoxyphenylthiazolidine moiety on the quinoxaline scaffold showed good bioactivity in all three assays.Graphical Abstract

Microwave synthesis, biological evaluation and docking studies of 2-substituted methyl 1-(4-fluorophenyl)-1H-benzimidazole-5-carboxylates

AbstractA library of 22 novel 2-substituted fluorinated benzimidazoles (5a-v) was synthesized under microwave conditions in yields of between 85–96% and tested for their antimicrobial and antioxidant activity. Two trioxygenated derivatives 5p and 5r had minimum bactericidal concentration values ranging between 14.5–115.7 μM (5p) and 25.6–74.3 μM (5r) against S. aureus, E. coli, P. aeruginosa and K. pneumoniae. The benzimidazole 5e with a CF3 substituent had the best antifungal activity at 94.3 µM against C. albicans. Compounds 5p and 5r also showed good antioxidant activities of 386.6 and 306.7 µM respectively, comparable to that of ascorbic acid. Docking studies of 5  h and 5r into the active site of topoisomerase II DNA-gyrase indicated that interaction with the Mn2+ ion in the active site of the enzyme was crucial for antibacterial activity.

Synthesis and structure elucidation using 2D NMR and thermal coefficient investigation on amino acid tethered quinoxalines.

1454–1458. [7] C. Almeida, N. E. Aouad, J. Martín, I. Pérez-Victoria, V. González-Menéndez, G. Platas, M. D. L. Cruz, M. C. Monteiro, N. D. Pedro, G. F. Bills, F. Vicente, O. Genilloud, F. Reyes. J. Antibiot. 2014, 67, 421–423. [8] K. Zou, J. Z. Wang, Z. Y. Guo, M. Du, J. Wu, Y. Zhou, F. J. Dan, C. Liu.Magn. Reson. Chem. 2009, 47, 87–91. [9] Z. Y. Guo, K. Zou, J. Z. Wang, C. Liu, Z. C. Tang, C. Y. Yang. Magn. Reson. Chem. 2009, 47, 613–616. [10] C. X. Liu, Z. Y. Guo, Y. H. Xue, H. Y. Zhang, H. Q. Zhang, K. Zou, N. Y. Huang. Magn. Reson. Chem. 2012, 50, 320–324. [11] X. C. Li, Z. Y. Guo, Z. S. Deng, J. Yang, K. Zou. Rec. Nat. Prod. 2015, 9, 503–508. [12] Y. Shiono, M. Kikuchi, T. Koseki, T. Murayama, E. Kwon, N. Aburai, K.-I. Kimura. Phytochemistry 2011, 72, 1400–1405. [13] L. Liu, H. Gao, X. L. Chen, X. Y. Cai, L. L. Yang, L. D. Guo, X. S. Yao, Y. S. Che. Eur. J. Org. Chem. 2010, 17, 3302–3306. [14] Z. Guo, F. X. Ren, Y. S. Che, G. Liu, L. Liu. Molecules 2015, 20, 14611–14620. [15] L. Liu, X. Y. Chen, D. Li, Y. Zhang, L. Li, L. D. Guo, Y. Cao, Y. S. Che. J. Nat. Prod. 2015, 78, 746–753. [16] S. X. Chen, Y. Zhang, S. B. Niu, X. Z. Liu, Y. S. Che. J. Nat. Prod. 2014, 77, 1513–1518. [17] S. X. Chen, Y. Zhang, C. Zhao, F. X. Ren, X. Z. Liu, Y. S. Che. Fitoterapia 2014, 99, 236–242. [18] I. E. Mohamed, S. Kehraus, A. Krick, G. M. König, G. Kelter, A. Maier, H.-H. Fiebig, M. Kalesse, N. P. Malek, H. Gross. J. Nat. Prod. 2010, 73, 2053–2056. [19] C. X. Liu, L. Wang, J. F. Chen, Z. Y. Guo, X. Tu, Z. S. Deng, K. Zou. Magn. Reson. Chem. 2015, 53, 317–322. [20] Y. Shiono, T. Hatakeyama, T. Murayama, T. Koseki. Nat. Prod. Commun. 2012, 7, 1065–1068. [21] L. Y. Wang, J. Wu, Z. Yang, X. J. Wang, Y. Fu, S. Z. Liu, H. M. Wang, W. L. Zhu, H. Y. Zhang, W. M. Zhao. J. Nat. Prod. 2013, 76, 745–749.