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4-Arylamino-6-nitroquinazolines ( 2 – 25 ) were synthesized and evaluated for their leishmanicidal activities against Leishmania major promastigotes in vitro with IC 50 values = 1.87–61.48 μ M. Among the twenty four synthetic derivatives, 4-[4′-(methylsulfanyl)phenyl]amino-6-nitroquinazoline ( 21 ), and 4-(2′-methoxyphenyl)amino-6-nitroquinazoline ( 8 ) showed excellent antileishmanial activities with IC 50 values 1.87 ± 0.31 and 4.37 ± 0.02 μ M, respectively, more active than the standard drug, pentamidine (IC 50 = 5.09 ± 0.09 μ M). Compound 16 (IC 50 = 6.53 ± 0.21 μ M) displayed an activity comparable to the standard. Compounds 15 (IC 50 = 9.04 ± 0.03 μ M), 18 (IC 50 = 12.28 ± 0.18 μ M), 14 (IC 50 = 19.87 ± 0.22 μ M), and 5 (IC 50 = 24.03 ± 2.71 μ M) also showed good activities. [ABSTRACT FROM AUTHOR]

Twenty-five derivatives of 2-arylquinazolin-4(3 H )-ones ( 1 – 25 ) were evaluated for their yeast (Saccharomyces cerevisiae) α-glucosidase inhibitory activities. All synthetic compounds, except 1 and 6 , were found to be several hundred fold more active (IC 50 values in the range of 0.3 ± 0.01–117.9 ± 1.76 μM), than the standard drug, acarbose (IC 50 = 840 ± 1.73 μM). The enzyme kinetic studies on the most active compounds 12 , 4 , 19 , and 13 were performed for the determination of their modes of inhibition and dissociation constants K i . Study of the modes of inhibition of compounds 12 , and 4 were also performed using molecular modeling techniques. In brief, current study identifies a novel class of α-glucosidase inhibitors which can be further studied for the treatment of hyperglycemia and obesity. [ABSTRACT FROM AUTHOR]

Abstract: 2-Arylquinazolin-4(3H)-ones 1–25 were synthesized by reacting anthranilamide with various benzaldehydes using CuCl2·2H2O as a catalyst in ethanol under reflux. Synthetic 2-arylquinazolin-4(3H)-ones 1–25 were evaluated for their β-glucuronidase inhibitory potential. A trend of inhibition IC50 against the enzyme in the range of 0.6–198.2μM, was observed and compared with the standard d-saccharic acid 1,4-lactone (IC50 =45.75±2.16μM). Compounds 13, 19, 4, 12, 14, 22, 23, 25, 15, 8, 17, 11, 21, 1, 3, 18, 9, 2, and 24 with the IC50 values within the range of 0.6–44.0μM, indicated that the compounds have superior activity than the standard. The compounds showed no cytotoxic effects against PC-3 cells. A structure–activity relationship is established. [Copyright &y& Elsevier]

[Display omitted] • SMS-IV-20 and SMS-IV-40 potently induce apoptosis in MCF-7 and MCF-7-CR cells. • The compounds chemo-sensitize MCF-7 and MCF-7-CR cells expressing MOAP-1, Bax, and RASSF1a. • When combine with ABT-737, both compounds enhance apoptotic cell death in MCF-7-CR cells. • The compounds down-regulate the expression of BCl-2, BCL-XL, or both in MCF-7-CR cells. Chemo-resistant cancer cells acquire robust growth potential through cell signaling mechanisms such as the down-regulation of tumor suppressors and the up-regulation of pro-survival proteins, respectively. To overcome chemo-resistance of cancer, small molecule drugs that interact with the cell signaling proteins to enhance sensitization of cancer cells toward cancer therapies are likely to be effective for the treatment of chemo-drug resistant cancer. To identify high potency small molecules, a series of ten novel phenylquinazoline derivatives were synthesized to determine their cellular effects in MCF-7 and MCF-7- cisplatin-resistant (CR) human breast cancer cells which led to the identification of two bioactive compounds, SMS-IV-20 and SMS-IV-40, that exhibited an elevated level of cytotoxicity against the human breast cancer cells and spheroid cells. In addition, both compounds enhanced chemo-sensitization of the human breast cancer cells that were genetically engineered to express the tumor suppressor and pro-apoptotic proteins, MOAP-1, Bax, and RASSF1a (MBR), suggesting that the compounds interact with the MBR signaling pathway. Furthermore, when MCF-7-CR cells were treated with SMS-IV-20 and SMS-IV-40 in the presence of ABT-737, a BCL-XL and BCL-2 inhibitor, enhanced chemo-sensitization was observed, suggesting SMS-IV-20 and SMS-IV-40 exert antagonistic activity to regulate the functional activity of BCL-2 and BCL-XL. Western blot analysis showed that both SMS-IV-20 and SMS-IV-40 induced down-regulation of BCL-2 or both BCl-2 and BCL-XL expression, respectively while promoting the release of mitochondrial Cytochrome C. Taken together, the data showed that SMS-IV-20 and SMS-IV-40 are potent activators of apoptosis that enhance chemo-sensitization through their antagonistic actions on the pro-survival activity of the BCl-2 family in human cancer cells. [ABSTRACT FROM AUTHOR]

• Rebar inspection & progress monitoring smart system. • Interpretation of point cloud models for quantitative rebar monitoring parameters. • Comparison of smart system outcomes with ground truth dimensions of rebar grid. Current rebar inspection practices in construction projects are manual in nature; hence, they are time-consuming. Rebar drawings are technical; therefore, the accuracy of inspection outcomes depends on the inspector's (supervisor or engineer) experience. In contrast, with the emergence of the fourth industrial revolution, the construction industry has also adopted a few technological solutions for rebar progress monitoring. However, most of the available solutions are detecting qualitative aspects, and quantitative aspects are not much covered. Moreover, available studies have focused on specific rebar monitoring parameters and have not given a complete solution. This study aims to develop an automated smart rebar evaluation model (SREM) giving a complete solution for evaluating on-site rebar quality (rebar spacing, rebar diameter) and quantity (number of rebars, rebar length). The devised system will be able to interpret the 3D point cloud model generated via photogrammetry for rebar quality and quantity parameters easily accessible by project stakeholders. The SREM has the capability to evaluate on-site rebar with the help of images with an accuracy of more than 99% for rebar length and the number of rebars, 97% for rebar spacing, and an accuracy of more than 90% for rebar diameter. The SREM offers an economical, effective, and efficient solution with minimum human involvement. It provides site safety, especially for high-rise buildings, remote progress monitoring to far projects, and minimizes CO 2 emission by controlling unnecessary site visits. Most importantly, it is an IoT-supported model. [ABSTRACT FROM AUTHOR]

We report one-pot synthesis of a series of new 3-aryl-8-methylquinazolin-4(3 H)-ones (QNZ) and their antimicrobial activity against Acanthamoeba castellanii belonging to T4 genotype. A library of fifteen synthetic derivatives of QNZs was synthesized, and their structural elucidation was performed by using nuclear magnetic resonance (NMR) spectroscopy and electron impact mass spectrometry (EI-MS). Elemental analyses and high-resolution mass spectrometry data of all derivatives were found to be in agreeable range. Amoebicidal assays performed at concentrations ranging from 50 to 100 μg/mL revealed that all derivatives of QNZ significantly decreased the viability of A. castellanii and QNZ 2 , 5 , 8 , and 13 were found to have efficient antiamoebic effects. Field emission scanning electron microscopy (FESEM) imaging of amoeba treated with compounds 5 and 15 showed that these compounds cause structural alterations on the walls of A. castellanii. Furthermore, several QNZs inhibited the encystation and excystationas as well as abolished A. castellanii -mediated host cells cytopathogenicity in human cells. Whereas, these QNZs showed negligible cytotoxicity when tested against human cells in vitro. Hence, this study identified potential lead molecules having promising properties for drug development against A. castellanii. A brief structure-activity relationship is also developed to optimize the hit of most potent compounds from the library. To the best of our knowledge, it is first of its kind medicinal chemistry approach on a single class of compounds i.e., quinazolinone against keratitis and brain infection causing free-living amoeba, A. castellanii. Image 1 • Acanthamoeba is an opportunistic parasite that can cause keratitis and encephalitis. • Quinazolinones hold promise in the drug development against infectious diseases. • 3-aryl-8-methylquinazolin-4(3 H)-ones were synthesized by varying aniline derivatives. • A series of fifteen new quinazolinone derivatives have been tested against A. castellanii for the first time. • These quinazolinone derivatives exhibited potent anti -acanthamoebic activity. [ABSTRACT FROM AUTHOR]

An efficient protocol has been developed for the one-pot synthesis of tetrazole derivatives in moderate to good yields starting from substituted benzaldehydes and proceeding via non-isolated oxime and nitrile intermediates. The structures of the desired products were confirmed by IR, and NMR spectroscopy as well as mass spectrometry. A plausible reaction mechanism is also discussed. [ABSTRACT FROM AUTHOR]

Oxadiazole derivatives ( 6 – 28 ) having hydrazone linkage, were synthesized through condensation reaction between benzohydrazide 5 with various benzaldehydes. The oxadiazoles derivatives ( 6 – 28 ) were evaluated for their α-glucosidase inhibitory activity. The IC 50 values for inhibition activity vary in the range between 2.64 ± 0.05 and 460.14 ± 3.25 μM. The IC 50 values were being compared to the standard acarbose (IC 50 = 856.45 ± 5.60 μM) and it was found that compounds 6 – 9 , 12 , 13 , 16 , 18 , 20 , 22 – 28 were found to be more active than acarbose, while other compounds showed no activity. Structure–activity relationship (SAR) studies suggest that oxadiazole benzohydrazones ( 6 – 28 ) inhibitory potential is dependent on substitution of the N -benzylidene part. Compound 18 (IC 50 = 2.64 ± 0.05 μM), which has trihydroxy substitution at C-2′, C-4′, and C-5′ on N -benzylidene moiety, recorded the highest inhibition activity that is three-hundred times more active than the standard drug, acarbose (IC 50 = 856.45 ± 5.60 μM). Compound 23 (IC 50 = 34.64 ± 0.35 μM) was found to be the most active among compounds having single hydroxyl substitution. Shifting hydroxyl from C-2′ to C-4′ ( 6 ) and C-3′ ( 7 ) reduces inhibitory activity significantly. Compounds with chlorine substituent (compounds 16 , 28 , and 27 ) showed potent activities but lower as compared to hydroxyl analogs. Substituent like nitro or methyl groups at any position suppresses enzyme inhibition activity. This reveals the important presence of hydroxyl and halo groups to have enzyme inhibitory potential. [ABSTRACT FROM AUTHOR]

A series of Schiff base triazoles 1 – 25 was synthesized and evaluated for their nucleotide pyrophosphatase/phosphodiesterase-1 inhibitory activities. Among twenty-five compounds, three compounds 10 (IC 50 = 132.20 ± 2.89 μM), 13 (IC 50 = 152.83 ± 2.39 μM), and 22 (IC 50 = 251.0 ± 6.64 μM) were identified as potent inhibitors with superior activities than the standard EDTA (IC 50 = 277.69 ± 2.52 μM). The newly identified inhibitors may open a new avenue for the development of treatment of phosphodiesterase-I related disorders. These compounds were also evaluated for carbonic anhydrase, acetylcholinesterase and butyrylcholinesterase inhibitory potential and were found to be inactive. The compounds showed non-toxic effect towards PC3 cell lines. [ABSTRACT FROM AUTHOR]

Oxadiazoles and thiadiazoles 1 – 37 were synthesized and evaluated for the first time for their α-glucosidase inhibitory activities. As a result, fifteen of them 1 , 4 , 5 , 7 , 8 , 13 , 17 , 23 , 25 , 30 , 32 , 33 , 35 , 36 and 37 were identified as potent inhibitors of the enzyme. Kinetic studies of the most active compounds (oxadiazoles 1 , 23 and 25 , and thiadiazoles 35 and 37 ) were carried out to determine their mode of inhibition and dissociation constants K i . The most potent compound of the oxadiazole series (compound 23 ) was found to be a non-competitive inhibitor ( K i = 4.36 ± 0.017 μM), while most potent thiadiazole 35 was identified as a competitive inhibitor ( K i = 6.0 ± 0.059 μM). The selectivity and toxicity of these compounds were also studied by evaluating their potential against other enzymes, such as carbonic anhydrase-II and phosphodiesterase-I. Cytotoxicity was evaluated against rat fibroblast 3T3 cell line. Interestingly, these compounds were found to be inactive against other enzymes, exhibiting their selectivity towards α-glucosidase. Inhibition of α-glucosidase is an effective strategy for controlling post-prandial hyperglycemia in diabetic patients. α-Glucosidase inhibitors can also be used as anti-obesity and anti-viral drugs. Our study identifies two novel series of potent α-glucosidase inhibitors for further investigation. [ABSTRACT FROM AUTHOR]

Background The ideal conditioning regimen still remains a challenge in the autologous stem cell transplantation (ASCT) setting for relapsed/refractory Hodgkin Lymphoma (RR-HL). BEAM is the most popular preparative regimen but single agent high dose Melphalan (HDM) has also been used. However, the experience and data comparing BEAM vs. HDM are limited. Methods After the Institutional Review Board approval, we retrospectively evaluated the clinical course of 112 RR-HL patients, autografted from November 2008 till May 2017 in two different institutions. Twenty eight conditioned with HDM and compared in a matched paired analysis (1:3) with a cohort of 84 patients who received BEAM. The study groups had similar median age (30ys) and sex (M:F 1.7:1 vs. 1.8:1) and were matched for disease status before salvage (late relapse: 36 vs. 12, early relapse/primary refractory: 48 vs. 16 and disease status pre ASCT [complete remission (CR): 39 vs. 13 and partial remission (PR): 45 vs. 15]. BEAM regimen was given in the standard doses over 6 days, while HDM (200mg/m2) was given in a single day infusion. All patients received prophylaxis against microbial, fungal and viral infections; GCSF was routinely administered at the dose of 5mcg/kg at +1 day (BEAM group) and at +5 day (HDM group). The T-test and Kaplan-Meier method were used for the statistical analyses. Results The engraftment was successful; the median day for neutrophils >1000/mm3 was +11 for both groups while for platelets >20000/mm3 a faster recovery was noticed for HDM group: +13 vs. +22 days (p<0.001). The median follow up for both groups is 2,5 years. In the BEAM group 64/84 patients are alive (49 disease free), and 23/ 28 from the HDM group are alive (20 disease free). In the whole cohort of patients the survival rates were superior in the HDM group thought not statistically significant; 5 years overall survival 65% vs. 80% and progression free survival 52% vs. 70% for the BEAM and HDM group respectively. The HDM regimen associated with better survival rates either for patients in CR or for those in PR before ASCT. The 100 days non relapse mortality was acceptable for both groups: 2/84 (2.3%) in the BEAM group vs. 1/28 (3.5%) in the HDM group. Conclusion In this study, though retrospective, demonstrated that for RR-HL patients, the conditioning regimen consisting of HDM, offered at least comparable efficacy to the BEAM regimen. The earlier platelets recovery, and the shorter duration of chemotherapy administration (6 days for BEAM vs. 1 day for HDM), resulted in less hospitalization days, which along with the shorter period of GCSF administration post ASCT, may contribute to a better cost effectiveness for the HDM regimen. Nevertheless, prospective studies with larger series of patients and longer follow-up, including also a meticulous cost analysis, are warranted to determine the accurate role of single agent HDM as preparative regimen for ASCT in HL patients. [ABSTRACT FROM AUTHOR]