2999-10-2Relevant academic research and scientific papers
Toward an efficient and eco-friendly route for the synthesis of dimeric 2,4-diacetyl phloroglucinol and its potential as a SARS-CoV-2 main protease antagonist: Insight from: In silico studies
Kusumaningsih, Triana,Prasetyo, Wahyu E.,Wibowo, Fajar R.,Firdaus, Maulidan
supporting information, p. 7830 - 7843 (2021/05/13)
As a consequence of the unavailability of an anti-viral drug for SARS-CoV-2, the prospect of developing an antiviral drug is of great importance in this current emergency of the COVID-19 pandemic era. To support the enduring research on the improvement of
Diacylphloroglucinol derivatives as antioxidant agents: green synthesis, optimisation, in?vitro, and in silico evaluation
Prasetyo, Wahyu E.,Kusumaningsih, Triana,Firdaus, Maulidan,Marliana, Soerya D.,Suryanti, Venty,Artanti, Anif N.,Apriana, Ita,Anggraini, Septin D.
supporting information, (2021/03/06)
Several derivatives of diacylphloroglucinol (3a–3c and 5a–5b) as an analogue of natural product compound 2,4-diacetylphloroglucinol 3a, were successfully synthesised in an excellent yield via a greener Friedel–Craft acylation using methanesulfonic acid (MSA) as a catalyst under an ultrasound-assisted condition. Operational simplicity, excellent yield, expedient metal-free synthesis, energy-efficient and mild reaction conditions are the outstanding advantages in this procedure. A scaled-up reaction also revealed the practical suitability of this newly developed procedure. The effects of several process variables on 3a were carefully accomplished using response surface methodology (RSM). Moreover, the green credentials of the present protocol have been assessed using several established green metrics and compared to relevant procedures. Along with the monomers, dimeric diacylphloroglucinols (6a–6e) were also synthesised and their in?vitro antioxidant activity of these species were carried out. Furthermore, drug-likeness, density functional theory (DFT), and molecular docking studies were also established.
A greatly improved procedure for the synthesis of an antibiotic-drug candidate 2,4-diacetylphloroglucinol over silica sulphuric acid catalyst: multivariate optimisation and environmental assessment protocol comparison by metrics
Firdaus, Maulidan,Kusumaningsih, Triana,Prasetyo, Wahyu Eko
, p. 31824 - 31837 (2020/09/17)
Efforts toward the development of a straightforward greener Gram-scale synthesis of the antibiotic compound 2,4-diacetylphloroglucinol (DAPG) have been developed. This beneficial procedure was accomplished through the Friedel-Crafts acylation of phloroglucinol over inexpensive heterogeneous silica sulphuric acid (SSA) catalystviaultrasound-assisted (US) synthesis under solvent-free condition. The influences of various parameters such as temperature, catalyst loading, and reaction time on the reaction performance were analysed using a multivariate statistical modelling response surface methodology (RSM). A high yield ofDAPG(95%) was achieved at 60 °C after 15-20 min reaction with the presence of 10% (w/w)SSAas the catalyst. Column chromatography-free and a Gram scale-up reaction also exhibited the practical applicability of this newly developed protocol. TheSSAcatalyst was recovered and recycled up to 10 consecutive runs with no appreciable loss of activity. A plausible mechanism for the Friedel-Crafts acylation of phloroglucinol is proposed. Moreover, an environmental assessment has been carried out over this present method and compared with several established literature using the EATOS software and the Andraos algorithm to assess the consumption of the substrates, solvents, catalysts, and the production of coupled products or by-products. In addition, their energy consumptions were also determined. The data collected showed that the present method is the most promising one, characterised by the highest environmental impact profile against all the other reported methods. The physicochemical properties of the synthesisedDAPGwere assessed and exhibited reasonable oral bioavailability drug property as determined by Lipinski's rules.
Highly efficient and green synthesis of diacylphloroglucinol over treated natural zeolite mordenite and the optimization using response surface method (RSM)
Prasetyo, Wahyu Eko,Kusumaningsih, Triana,Firdaus, Maulidan
supporting information, p. 3352 - 3372 (2019/11/11)
Herein, we report a greener and highly efficient route for the Friedel-Craft acylation of phloroglucinol over Indonesian treated natural zeolite mordenite (nHZMOR) catalyst to provide value-added diacylphloroglucinol derivatives under solvent-free conditi
2. 4 - Diacetyl phloroglucinol analogue and its preparation method and application
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Paragraph 0024; 0031; 0050, (2018/05/30)
The invention discloses a 2,4-DAPG analogue and a preparation method and application thereof. The structure of the 2,4-DAPG analogue is shown as the formula (1) or formula (2), wherein R is C2-C15 alkyl, R1 and R2 are C1-C15 alkyl, and the R1 and the R2 a
Synthesis and P-glycoprotein induction activity of colupulone analogs
Bharate, Jaideep B.,Batarseh, Yazan S.,Wani, Abubakar,Sharma, Sadhana,Vishwakarma, Ram A.,Kaddoumi, Amal,Kumar, Ajay,Bharate, Sandip B.
, p. 5488 - 5496 (2015/05/20)
Brain amyloid-beta (Aβ) plaques are one of the primary hallmarks associated with Alzheimer's disease (AD) pathology. Efflux pump proteins located at the blood-brain barrier (BBB) have been reported to play an important role in the clearance of brain Aβ, among which the P-glycoprotein (P-gp) efflux transporter pump has been shown to play a crucial role. Thus, P-gp has been considered as a potential therapeutic target for treatment of AD. Colupulone, a prenylated phloroglucinol isolated from Humulus lupulus, is known to activate pregnane-X-receptor (PXR), which is a nuclear receptor controlling P-gp expression. In the present work, we aimed to synthesize and identify analogs of colupulone that are potent P-gp inducer(s) with an ability to enhance Aβ transport across the BBB. A series of colupulone analogs were synthesized by modifications at both prenyl as well as acyl domains. All compounds were screened for P-gp induction activity using a rhodamine 123 based efflux assay in the P-gp overexpressing human adenocarcinoma LS-180 cells, wherein all compounds showed significant P-gp induction activity at 5 μM. In the western blot studies in LS-180 cells, compounds 3k and 5f were able to induce P-gp as well as LRP1 at 1 μM. The effect of compounds on the Aβ uptake and transport was then evaluated. Among all tested compounds, diprenylated acyl phloroglucinol 5f displayed a significant increase (29%) in Aβ transport across bEnd3 cells grown on inserts as a BBB model. The results presented here suggest the potential of this scaffold to enhance clearance of brain Aβ across the BBB and thus its promise for development as a potential anti-Alzheimer agent.
Tandem one-pot synthesis of flavans by recyclable silica-HClO4 catalyzed Knoevenagel condensation and [4 + 2]-Diels-Alder cycloaddition
Bharate, Sandip B.,Mudududdla, Ramesh,Bharate, Jaideep B.,Battini, Narsaiah,Battula, Satyanarayana,Yadav, Rammohan R.,Singh, Baldev,Vishwakarma, Ram A.
experimental part, p. 5143 - 5150 (2012/08/08)
An efficient one-pot multi-component synthesis of flavans using perchloric acid supported on silica as a recyclable heterogeneous catalyst has been described. This is the first report of direct one-step construction of a flavan skeleton from a phenolic precursor. The method involves a Knoevenagel-type condensation leading to in situ formation of transient O-quinone methide which further undergoes [4 + 2]-Diels-Alder cycloaddition with styrene to yield a flavan skeleton. The method provides easy access to a wide range of bio-active natural products viz. flavonoids, anthocyanins and catechins.
Ortho-amidoalkylation of phenols via tandem one-pot approach involving oxazine intermediate
Mudududdla, Ramesh,Jain, Shreyans K.,Bharate, Jaideep B.,Gupta, Ajai P.,Singh, Baldev,Vishwakarma, Ram A.,Bharate, Sandip B.
, p. 8821 - 8827 (2012/11/07)
A new and efficient method for ortho-amidoalkylation of phenols via Mannich-type condensation with formaldehyde and lactams using recyclable solid acid catalyst is described. This is the first report for ortho-amidoalkylation of phenols by lactams via Mannich-type condensation. LC-ESI-MS/MS based mechanistic study revealed that reaction proceeds through o-quinone methide (o-QM) and an oxazine intermediate via tandem Knoevenagel condensation, formal [4 + 2]-Diels-Alder cycloaddition and acid catalyzed oxazine ring-opening.
One pot synthesis and anticancer activity of dimeric phloroglucinols
Chauthe, Siddheshwar K.,Bharate, Sandip B.,Periyasamy, Giridharan,Khanna, Amit,Bhutani, Kamlesh K.,Mishra, Prabhu D.,Singh, Inder P.
experimental part, p. 2251 - 2256 (2012/05/04)
A series of dimeric phloroglucinol compounds were synthesized in a single step using commercially available phloroglucinol and methanesulfonic acid. Based on the reported anticancer activity of plant derived dimeric phloroglucinols, these synthesized comp
Biomimetic synthesis and anti-HIV activity of dimeric phloroglucinols
Chauthe, Siddheshwar K.,Bharate, Sandip B.,Sabde, Sudeep,Mitra, Debashis,Bhutani, Kamlesh K.,Singh, Inder P.
body text, p. 2029 - 2036 (2010/06/12)
Plants are an important source of a variety of bioactive compounds with different modes of action. Anti-HIV agents from plant sources can be useful in developing novel therapies for inhibiting HIV infection. Based on the reported anti-HIV activity of plant derived phloroglucinols, several new dimeric phloroglucinols were synthesized in the present study by varying substitution on aromatic ring and at methylene bridge. Some of the synthesized compounds have shown good HIV inhibitory activity in a human CD4+ T cell line (CEM-GFP) infected with HIV-1 NL4.3 virus isolate. Structure-activity studies indicate that phenyl, 4-benzyloxy-1-phenyl and cyclohexyl substitution at methylene bridge gave compounds with better anti-HIV activity. Compounds 22 and 24 showed highest anti-HIV activity with an IC50 of 0.28 μM and 2.71 μM, respectively, former was more active than the positive standard AZT in cell based assay.
