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A series of novel α-furfuryl-2-alkylaminophosphonates have been efficiently synthesized from the one-pot three-component classical Kabachnik-Fields reaction in a green chemical approach by addition of an in situ generated dialkylphosphite to Schiff's base of aldehydes and amines by using environmental and eco-friendly silica gel supported iodine as a catalyst by microwave irradiation. The advantage of this protocol is simplicity in experimental procedures and products were resulted in high isolated yields. The synthesized α-furfuryl-2-alkylaminophosphonates were screened to in vitro antioxidant and plant growth regulatory activities and some are found to be potent with antioxidant and plant growth regulatory activities. These in vitro studies have been further supported by ADMET (absorption, distribution, metabolism, excretion, and toxicity), quantitative structure-activity relationship, molecular docking, and bioactivity studies and identified that they were potentially bound to the GLN340 amino acid residue in chain C of 1DNU protein and TYR597 amino acid residue in chain A of 4M7E protein, causing potential exhibition of antioxidant and plant growth regulatory activities. Eventually, title compounds are identified as good blood-brain barrier (BBB)-penetrable compounds and are considered as proficient central nervous system active and neuroprotective antioxidant agents as the neuroprotective property is determined with BBB penetration thresholds. © 2021 The Authors. Published by American Chemical Society.

A series of 3-amino-2-hydroxybenzofused 2-phosphalactones (4a-l) has been synthesized from the Kabachnik-Fields reaction via a facile route from a one-pot three-component reaction of diphenylphosphite with various 2-hydroxybenzaldehyes and heterocyclic amines in a new way of expansion. The in vitro anti-cell proliferation studies by MTT assay have revealed them as potential Panc-1, Miapaca-2, and BxPC-3 pancreatic cell growth inhibitors, and the same is supported by molecular docking, QSAR, and ADMET studies. The MTT assay of their SAHA derivatives against the same cell lines evidenced them as potential HDAC inhibitors and identified 4a, 4b, and 4k substituted with 1,3-thiazol, 1,3,4-thiadiazol, and 5-sulfanyl-1,3,4-thiadiazol moieties on phenyl and diethylamino phenyl rings as potential ones. Additionally, the flow cytometric analyses of 4a, 4b, and 4k against BxPC-3 cells revealed compound 4k as a lead compound that arrests the S phase cell cycle growth at low micromolar concentrations. The ADMET properties have ascertained their inherent pharmacokinetic potentiality, and the wholesome results prompted us to report it as the first study on anti-pancreatic cancer activity of cyclic α-aminophosphonates. Ultimately, this study serves as a good contribution to update the existing knowledge on the anticancer organophosphorus heterocyclic compounds and elevates the scope for generation of new anticancer drugs. Further, the studies like QSAR, drug properties, toxicity risks, and bioactivity scores predicted for them have ascertained the synthesized compounds as newer and potential drug candidates. Hence, this study had augmented the array of α-aminophosphonates by adding a new collection of 3-amino-2-hydroxybenzofused 2-phosphalactones, a class of cyclic α-aminophosphonates, to it, which proved them as potential anti-pancreatic cancer agents. ©

Phytochemicals of Christia vespertilionis plant is known for medicinal properties and used to treat various health problems. The present study revealed medicinal properties of the leaf extract of Christia vespertilionis plant as its total phenolic content derived is screened for their antioxidant, antidiabetic and toxicity properties by Folin-Ciocalteu method, DPPH assay with butylated hydroxytoluene standard, α-amylase inhibition assay with metformin standard, brine shrimp lethality bioassay respectively.

Acridone based synthetic and natural products with inherent anticancer activity advancing the research and generating a large number of structurally diversified compounds. In this sequence we have designed, synthesized a series of tetracyclic acridones with amide framework viz., 3-(alkyloyl/ aryloyl/ heteroaryloyl/ heteroaryl)-2,3-dihydropyrazino[3,2,1-de]acridin-7(1H)-ones and screened for their in vitro anti-cancer activity. The in vitro study revealed that compounds with cyclopropyl-acetyl, benzoyl, p-hydroxybenzoyl, p-(trifluoromethyl)benzoyl, p-fluorobenzoyl, m-fluorobenzoyl, picolinoyl, 6-methylpicolinoyl and 3-nicotinoyl groups are active against HT29, MDAMB231 and HEK293T cancer cell lines. The molecular docking studies performed for them against 4N5Y, HT29 and 2VWD revealed the potential ligand–protein binding interactions among the neutral aminoacid of the enzymes and carbonyl groups of the title compounds with a binding energy ranging from − 8.1394 to − 6.9915 kcal/mol. In addition, the BSA protein binding assay performed for them has confirmed their interaction with target proteins through strong binding to BSA macromolecule. The additional studies like ADMET, QSAR, bioactivity scores, drug properties and toxicity risks ascertained them as newer drug candidates. This study had added a new collection of piperazino fused acridone derivatives to the existing array of other nitrogen heterocyclic fused acridone derivatives as anticancer agents. © 2020, The Author(s).

A series of 1-(2,3-dihydro-1H-indan-1-yl)-3-aryl urea/thiourea derivatives (4a-j) have been synthesized from the reaction of 2,3-dihydro-1H-inden-1-amine (2) with various aryl isocyanates/isothiocyanates (3a-j) by using N,N-DIPEA base (Hunig's base) catalyst in THF at reflux conditions. All of them are structurally confirmed by spectral (IR, 1H & 13C NMR and MASS) and elemental analysis and screened for their in-vitro antioxidant activity against DPPH and NO free radicals and found that compounds 4b, 4i, 4h & 4g are potential antioxidants. The obtained in vitro results were compared with the molecular docking, ADMET, QSAR and bioactivity study results performed for them and identified that the recorded in silico binding affinities were observed in good correlation with the in vitro antioxidant results. The Molecular docking analysis had unveiled the strong hydrogen bonding interactions of synthesized ligands with ARG 160 residue of protein tyrosine kinase (2HCK) enzyme and plays an effective role in its inhibition. Toxicology studies have assessed the potential risks of 4a-j and inferred that all of them were in the limits of potential drugs. The conformational analysis of 4a-j inferred that the urea/thiourea spacer linking 2,3-dihydro-1H-inden-1-amino and substituted aryl units has facilitated all these molecules to effectively bind with ARG 160 amino acid residue present on the α-helix of the protein tyrosine kinase (2HCK) enzyme specifically on chain A of hemopoetic cell kinase. Collectively this study has established a relationship between the antioxidant potentiality and ligands binding with ARG 160 amino acid residue of chain A of 2HCK enzyme to inhibit its growth as well as proliferation of reactive oxygen species in vivo. © 2019 Elsevier Inc.

Background: Various randomized-controlled clinical trials (RCTs) have investigated the neuroprotective role of minocycline in acute ischemic stroke (AIS) or acute intracerebral hemorrhage (ICH) patients. We sought to consolidate and investigate the efficacy and safety of minocycline in patients with acute stroke. Methods: Literature search spanned through November 30, 2017 across major databases to identify all RCTs that reported following efficacy outcomes among acute stroke patients treated with minocycline vs. placebo: National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin Scale (mRS) scores. Additional safety, neuroimaging and biochemical endpoints were extracted. We pooled mean differences (MD) and risk ratios (RR) from RCTs using random-effects models. Results: We identified 7 RCTs comprising a total of 426 patients. Of these, additional unpublished data was obtained on contacting corresponding authors of 5 RCTs. In pooled analysis, minocycline demonstrated a favorable trend towards 3-month functional independence (mRS-scores of 0–2) (RR = 1.31; 95% CI 0.98–1.74, p = 0.06) and 3-month BI (MD = 6.92; 95% CI − 0.92, 14.75; p = 0.08). In AIS subgroup, minocycline was associated with higher rates of 3-month mRS-scores of 0–2 (RR = 1.59; 95% CI 1.19–2.12, p = 0.002; I2 = 58%) and 3-month BI (MD = 12.37; 95% CI 5.60, 19.14, p = 0.0003; I2 = 47%), whereas reduced the 3-month NIHSS (MD − 2.84; 95% CI − 5.55, − 0.13; p = 0.04; I2 = 86%). Minocycline administration was not associated with an increased risk of mortality, recurrent stroke, myocardial infarction and hemorrhagic conversion. Conclusions: Although data is limited, minocycline demonstrated efficacy and seems a promising neuroprotective agent in acute stroke patients, especially in AIS subgroup. Further RCTs are needed to evaluate the efficacy and safety of minocycline among ICH patients. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

Background: Pyrimethamine and sulfadiazine (P-S) combination is effective and considered the mainstay therapy for cerebral toxoplasmosis (CT). Alternative treatment regimens are available, but their relative efficacy and tolerability are not well known. Particularly, trimephoprim-sulfamethaxozole (TMP-SMX) shows potential advantages (i.e., tolerability, posology, parenteral formulation, cost, and accessibility) but its use is infrequent when P-S is available. Methods: We searched PubMed and 4 other databases to identify randomized controlled trials (RCTs) and cohort studies comparing different regimens for the treatment of HIV-associated CT. Two independent reviewers searched and identified studies and extracted data. Risk ratios (RRs) were pooled across studies using random-effects models. Results: Nine studies were included (5 RCTs, 3 retrospective cohorts, 1 prospective cohort). Treatment with P-S has the same or better clinical efficacy than P-C or TMP-SMX in terms of partial or complete response clinical response (P-C vs P-S: RR 0.87, 95%CI 0.70-1.08; TMP-SMX vs P-S: RR 0.97, 95%CI 0.78-1.21) and radiological response (P-C vs P-S: RR 0.92, 95%CI 0.82-1.03). Safety profile in terms of skin rash (P-C vs P-S: RR 0.81, 95%CI 0.56-1.17; TMP-SMX vs P-S: RR 0.17, 95%CI 0.02-1.29), liver impairment (P-C vs P-S: RR 0.48, 95%CI 0.24-0.97) and drug discontinuation due to adverse events (P-C vs P-S: RR 0.32, 95%CI 0.07-1.47) were worse with P-S regimen. Conclusion: The available evidence fails to identify any one superior regimen for the treatment of CT. However, P-S regimen has worse safety profile than P-C or TMP-SMX. Although current evidence does not allow a definitive recommendation, use of TMP-SMX for treatment of HIV-associated CT is consistent with the available data. More large studies comparing alternative therapies are needed., IDWeek, Evento que se llevó a cabo del 7 -11 de Octubre de 2015, en la ciudad de San Diego, CA, EE.UU. Evento Sesión HIV: Other Opportunistic Infections in HIV. Saturday, October 10, 2015. Room: Poster Hall

Background: Pyrimethamine and sulfadiazine (P-S) combination is effective and considered the mainstay therapy for cerebral toxoplasmosis (CT). Alternative treatment regimens are available, but their relative efficacy and tolerability are not well known. Particularly, trimephoprim-sulfamethaxozole (TMP-SMX) shows potential advantages (i.e., tolerability, posology, parenteral formulation, cost, and accessibility) but its use is infrequent when P-S is available. Methods: We searched PubMed and 4 other databases to identify randomized controlled trials (RCTs) and cohort studies comparing different regimens for the treatment of HIV-associated CT. Two independent reviewers searched and identified studies and extracted data. Risk ratios (RRs) were pooled across studies using random-effects models. Results: Nine studies were included (5 RCTs, 3 retrospective cohorts, 1 prospective cohort). Treatment with P-S has the same or better clinical efficacy than P-C or TMP-SMX in terms of partial or complete response clinical response (P-C vs P-S: RR 0.87, 95%CI 0.70-1.08; TMP-SMX vs P-S: RR 0.97, 95%CI 0.78-1.21) and radiological response (P-C vs P-S: RR 0.92, 95%CI 0.82-1.03). Safety profile in terms of skin rash (P-C vs P-S: RR 0.81, 95%CI 0.56-1.17; TMP-SMX vs P-S: RR 0.17, 95%CI 0.02-1.29), liver impairment (P-C vs P-S: RR 0.48, 95%CI 0.24-0.97) and drug discontinuation due to adverse events (P-C vs P-S: RR 0.32, 95%CI 0.07-1.47) were worse with P-S regimen. Conclusion: The available evidence fails to identify any one superior regimen for the treatment of CT. However, P-S regimen has worse safety profile than P-C or TMP-SMX. Although current evidence does not allow a definitive recommendation, use of TMP-SMX for treatment of HIV-associated CT is consistent with the available data. More large studies comparing alternative therapies are needed., IDWeek, Evento que se llevó a cabo del 7 -11 de Octubre de 2015, en la ciudad de San Diego, CA, EE.UU. Evento Sesión HIV: Other Opportunistic Infections in HIV. Saturday, October 10, 2015. Room: Poster Hall