Construction and functionalization of pyranone ring fused with pyran moiety: Design and synthesis of novel pyrano[4,3-b]pyran-5(4H)-ones as potential inhibitors of sirtuins

Nakhi, Ali; Rahman, Md. Shafiqur; Archana, Sivakumar; Kishore, Ravada; Seerapu, Guru Pavan Kumar; Kumar, K. Lalith; Haldar, Devyani; Pal, Manojit

doi:10.1016/j.bmcl.2013.05.014

Cited by 26 publications

(9 citation statements)

References 20 publications

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“…12) The bromo derivative 4k was synthesized through a Sandmeyer reaction 13) using the corresponding aniline 4k′ as a precursor. Finally, the Ndeprotection of pyrrole 4l′ was achieved after applying the reductive conditions described by Sajiko et al, 14) which afforded the pyrroloisoquinoline 4l.…”

Section: Resultsmentioning

confidence: 99%

5,6-Dihydropyrrolo[2,1-<i>a</i>]isoquinolines as Alternative of New Drugs with Cytotoxic Activity

Chávez-Santos

Reyes‐Gutiérrez

Torres‐Ochoa

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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In this study, the pyrrolo[2,1-a] isoquinolines 4a-n were synthesized in good yields in a three steps synthesis from the corresponding α,β-unsaturated esters starting materials. These compounds were tested on six human cancer cells lines to measure the cytotoxic activity as a function of the electronic properties and aromaticity of the substituent at the C-2 position of the pyrroloisoquinoline. Our results reveal that the cytotoxic activity could be explained in terms of the distribution of electronic density across the ring joined to C-2. Also, this study identified 3-hydroxy (4d) and 3-chloro (4j) derivatives with powerful cytotoxic activities. The IC 50 values of these compounds were found to be comparable to those of the commercially available Topotecan, Irinotecan, Etoposide, Tamoxifen, and Cisplatin.Key words pyrrolo[2,1-a]isoquinoline; synthesis; cytotoxic activity Cancer is a leading cause of death worldwide, and according to the World Cancer Research Fund International (GLOBOCAN 2012), an estimated 17.1 million new cancer cases and 10.0 million cancer-related deaths will occur in 2020, compared with 15.2 million and 8.9 million, respectively, in 2015.1) The most commonly diagnosed cancers worldwide are cancers of the skin (melanoma), prostate, lung, breast, and colorectum.2) Cancer poses a challenge to researchers searching for potent drugs that are capable of controlling cancer growth while minimizing side effects or the development of drug resistance. Our group is currently engaged in a program aimed at synthesizing novel heterocyclic compounds that inhibit the growth of cancer cells. We recently synthesized the pyrroloisoquinolines I-IV 3,4) ( Table 1) in a threestep protocol, and their cytotoxic activities were tested on six tumor cell lines: PC-3 (human prostatic adenocarcinoma), U-251 (human glioblastoma), K-562 (human chronic myelogenous leukemia), HCT-15 (human colorectal adenocarcinoma), MCF-7 (human mammary adenocarcinoma), and SKLU-1 (human lung adenocarcinoma). The results of this study (Table 1), allowed us to establish preliminary structure-activity relationship (Fig. 1) that revealed the importance of the aromatic substituent at the C-2 position, particularly when the substituent was a m-(cyclohexylmethylpiperazinamide)phenyl (I), phenyl (II), or m-(amino) phenyl (III), substituent, in combination with an ethyl ester at the C-1 position. Following up on these preliminary structure-activity studies, the present work sought to synthesize the novel pyrroloisoquinolines 4a-c (Fig. 2) to evaluate the effects of modifying the cyclohexylmethylpiperazinyl moiety on the antiproliferative activity. Compounds 4d-k (Fig. 2) were evaluated to determine the role of the phenyl ring substituent on the antiproliferative activity of the compound. Compounds 4l-n (Fig. 2) were evaluated to determine the effect of modifying the aromaticity of the C-2 substituent on the antiproliferative activity. Results and DiscussionChemistry The synthetic route to compounds 4a-n is depicted in Chart 1. Compounds 4a-n wer...

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Section: Resultsmentioning

confidence: 99%

5,6-Dihydropyrrolo[2,1-<i>a</i>]isoquinolines as Alternative of New Drugs with Cytotoxic Activity

Chávez-Santos

Reyes‐Gutiérrez

Torres‐Ochoa

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Xanthenes, in particular, 1,8-dioxo-octahydroxanthene moieties, have gained significant attention due to their potent pharmacological efficacies, such as anti--microbial, anti-cancer and enzyme inhibitory activity. [94][95][96] Another efficient protocol was developed for the synthesis of 2,3-dihydro-1Hxanthen-1-one derivatives (61) via the cycloaddition of 1,3-cyclohexanediones (37b or 37b′) and salicylaldehyde (44) using glycine as promoter in [bmim]PF 6 at 25 °C (Scheme 23). 98 Conventional solvents, such as acetonitrile, DMF, DMSO, etc., were also screened for this reaction but lower yields were attained.…”

Section: Synthesis Of Xanthenesmentioning

confidence: 99%

[Bmim]PF6: An efficient tool for the synthesis of diverse bioactive heterocycles

Kaur¹,

Sharma²,

Banerjee³

2018

JSCS

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Heterocycles are the privileged structural subunit of many marketed drug molecules. On the other hand, the last decade has seen tremendous applications of the ionic liquid [bmim]PF 6 (1-butyl-3-methyl-1H-imidazolium hexafluorophosphate) as an efficient, cheap, commercially available, low toxic reaction medium for various organic transformations. The present review summarizes recent reported applications of [bmim]PF 6 as an efficient reaction medium for the synthesis of diverse biologically relevant heterocycles.

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“…Xanthenes, in particular, 1,8-dioxo-octahydroxanthene moieties, have received significant attention due to their potent pharmacological efficacies such as antimicrobial, anticancer and enzyme inhibitory activity [110][111][112]. Recently, Safaei-Ghomi et al have synthesized a variety of structurally diverse xanthene derivatives using ZnO-nanoparticles as catalyst.…”

Section: Synthesis Of Xanthenesmentioning

confidence: 99%

Recent developments on nano-ZnO catalyzed synthesis of bioactive heterocycles

Banerjee

2017

J Nanostruct Chem

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Last decade has seen tremendous applications of nano-ZnO as a mild, cheap, efficient, commercially available, environmentally benign, non-toxic, reusable, heterogeneous catalyst for the various organic transformations. The present review summarizes the applications of nano-ZnO as an efficient heterogeneous catalyst for the synthesis of diverse biologically relevant heterocycles reported so far. Graphical abstract Nano

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Construction and functionalization of pyranone ring fused with pyran moiety: Design and synthesis of novel pyrano[4,3-b]pyran-5(4H)-ones as potential inhibitors of sirtuins

Cited by 26 publications

References 20 publications

5,6-Dihydropyrrolo[2,1-<i>a</i>]isoquinolines as Alternative of New Drugs with Cytotoxic Activity

5,6-Dihydropyrrolo[2,1-<i>a</i>]isoquinolines as Alternative of New Drugs with Cytotoxic Activity

[Bmim]PF6: An efficient tool for the synthesis of diverse bioactive heterocycles

Recent developments on nano-ZnO catalyzed synthesis of bioactive heterocycles

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