Design and synthesis of novel triazolo-lapatinib hybrids as inhibitors of breast cancer cells
AbstractA series of triazolo-lapatinib hybrids were synthesized via copper (II)-oxide nanoparticle (Cu2O-NP)-catalyzed azide-alkyne cycloaddition. The ability of these compounds to reduce the viability of breast cancer SKBR3 and SUM159 cells and stem cell-like KG-1a leukemia cells was subsequently evaluated. Compared with lapatinib, compounds6c–f were more potent than lapatinib against the three cell lines. Next, the toxicity of compounds6c–f was assessed in zebrafish. Compound6d had comparable toxicity with lapatinib at 200  μM (mortality rate = 10 vs. 10%), and compound6e had lower tox...
Source: Medicinal Chemistry Research - November 1, 2018 Category: Chemistry Source Type: research

Synthesis and antiviral study of novel 4-(2-(6-amino-4-oxo-4,5-dihydro-1H-pyrrolo[2,3-d]pyrimidin-3-yl)ethyl)benzamide derivatives
AbstractA series of ten new compounds (7a –j) has been synthesized by absolutely replacing the glutamic acid part of Pemetrexed drug, chemically known as N-{4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-l-glutamic acid, with primary, secondary, and aryl amines in high yields using diethylphosphorocyanidate (DEPC) as a peptide coupling agent. All the synthesized compounds are characterized by1H and13C NMR, LCMS, and FT-IR spectral techniques. All the synthesized novel non-glutamate 4-(2-(6-amino-4-oxo-4,5-dihydro-1H-pyrrolo[2,3-d]pyrimidin-3-yl)ethyl)benzamide derivatives showed 4- to ...
Source: Medicinal Chemistry Research - October 27, 2018 Category: Chemistry Source Type: research

Synthesis and spectroscopic analysis of benzylidene imidazolone linked to P-porphyrins through axial ligand
AbstractTetraphenylporphyrinatophosphorus(V) complexes (1) comprising two axially linked benzylidene imidazolone (Biz) moieties, which are chromophores of the green fluorescent protein, were prepared. In medical applications such as photodynamic therapy, the P-porphyrin part (Ptp) is expected to sensitize to generate singlet oxygen, whereas the Biz units act as fluorescent probes. The fluorescence spectra of1 were analyzed under the excitations of Biz at 370  nm. Fluorescence stemming from the excited states of Biz and Ptp was observed at 460 and 610 nm, respectively. The intramolecular quenching of Biz in th...
Source: Medicinal Chemistry Research - October 27, 2018 Category: Chemistry Source Type: research

Synthesis, antitrypanosomal activity and molecular docking studies of pyrimidine derivatives
AbstractThis publication describes the synthesis of 28 pyrimidine derivatives of which eight are new. Their structures have been verified by spectroscopic techniques (IR, H1, C13 NMR data). The mass spectral analysis gave correctly the elemental compositions of all compounds. All 28 compounds have been evaluatedin vitro against two different stages ofTrypanosoma cruzi: 1. epimastigote and 2. trypomastigotes. Compounds3a,3b,3j,3k,3o,3s and5d presented greater activity than benznidazole(BZN) for trypomastigotes. Compound 3a selectivity was similar to that of BZN. Molecular modeling using the Docking approach was performed to...
Source: Medicinal Chemistry Research - October 26, 2018 Category: Chemistry Source Type: research

Antioxidant properties of Calendula officinalis L. (Asteraceae) on Fe 2+ -initiated peroxidation of rat brain mitochondria
AbstractIn the study reported here, the effect ofCalendula officinalis L. (Asteraceae) extract (CO) on the polyunsaturated fatty acid composition, chemiluminescence, and Peroxidizability Index (PI) of mitochondria isolated from brain rat was analyzed. After incubation of mitochondria in an ascorbate (0.4  mM)-Fe++ (2.15  µM) system (180 min at 37 °C), it was observed that the total cpm/mg protein originated from light emission: chemiluminescence was lower in brain mitochondria obtained from CO group than in the control group (without extract supplementation). Moreover, it was observed ...
Source: Medicinal Chemistry Research - October 26, 2018 Category: Chemistry Source Type: research

Uses of dimedone for the synthesis of thiazole derivatives as new anti-tumor, c-Met, tyrosine kinase, and Pim-1 inhibitions
AbstractA series of heterocyclic compounds derived from dimedone were synthesized through the first reaction of dimedone with elemental sulfur and phenylisothiocyanate followed by heterocyclization of the produced thiazole derivative through its reaction with different chemical reagents. All the synthesized compounds were determined by elemental analysis,1H NMR,13C NMR, and MS. The newly synthesized compounds were evaluated for their in vitro cytotoxic activity against c-Met kinase, and the six typical cancer cell lines (A549, H460, HT-29, MKN-45, U87MG, and SMMC-7721). All target compounds were initially tested for their ...
Source: Medicinal Chemistry Research - October 20, 2018 Category: Chemistry Source Type: research

Diazabenzo[a]phenoxazone sulphonamides: synthesis, in-silico and in-vitro antimicrobial studies
AbstractThe syntheses of new sulphonamide derivatives of 8,10-diazabenzo[a]phenoxazones are reported. The condensation of 4,5-diamino-6-hydroxy-2-mercaptopyrimidine and 2,3-dichloro-1,4-naphthoquinone in a basic medium gave the key functional intermediate, 11-amino-6-chloro-9-mercapto-8,10-diazabenzo[a]phenoxazin-5-one. The conversion of the later compound to its sulphonamide derivatives was achieved via nickel catalyzed cross-coupling Buchwald-Hartwig protocol. Reaction between 11-amino-6-chloro-9-mercapto-8,10-diazabenzo[a]phenoxazin-5-one and various aryl sulphonamides and sulphonyl chlorides furnished eight new mono su...
Source: Medicinal Chemistry Research - October 10, 2018 Category: Chemistry Source Type: research

QSAR studies of new pyrido[3,4- b ]indole derivatives as inhibitors of colon and pancreatic cancer cell proliferation
AbstractWe have discovered a new class of pyrido[b]bindole derivatives that show potent and broad spectrum anticancer activity with IC50 values down to submicromolar levels. Structure –activity relationship data acquired with the compounds as antiproliferative agents against several cancer cell lines, i.e., human HCT116 colon cancer cell line, HPAC and Mia-PaCa2 pancreatic cancer cell lines, were subjected to two different QSAR modeling methods. A kernel-based partial least squ ares (KPLS) regression analysis with chemical 2D fingerprint descriptors, and a PHASE pharmacophore alignment with 3D-QSAR study. The KPLS me...
Source: Medicinal Chemistry Research - October 3, 2018 Category: Chemistry Source Type: research

Cytotoxicity, apoptosis, and QSAR studies of phenothiazine derived methoxylated chalcones as anticancer drug candidates
AbstractIn the present study, chalcones “(E)-1-(10H-phenothiazine-2-yl)-3-aryl-prop-2-en-1-ones,FS1-11” were successfully synthesized via base-catalyzed Claisen–Schmidt condensation. Chemical structures of the compounds were confirmed by1H NMR,13C NMR, and HRMS techniques. Aryl part of the chalcone was changed as mono, di, and trimethoxylated phenyls. Cytotoxicities of the phenothiazine derivatives were evaluated against four human oral squamous cell carcinoma (OSCC) cell lines (Ca9-22, HSC-2, HSC-3, and HSC-4) and three human normal oral cells (HGF, HPLF, and HPC) by MTT test. The CC50 values of the comp...
Source: Medicinal Chemistry Research - October 1, 2018 Category: Chemistry Source Type: research

Design, synthesis and biological evaluation of quinoxaline N -propionic and O -propionic hydrazide derivatives as antibacterial and antifungal agents
AbstractNovel series of quinaxoline derivatives incorporatingN-propionic andO-propionic hydrazide moieties were synthesized. Alkylation of 3-methylquinoxalin-2(1H)-one with ethyl 2-bromopropanoate afforded a mixture ofO-alkylated andN-alkylated 3-methylquinoxaline. Hydrazide derivatives were afforded by reaction ofO-alkylated andN-alkylated 3-methylquinoxaline with hydrazine hydrate. Condensation of hydrazide derivatives with different aromatic aldehydes and formylpyrazoles afforded the corresponding hydrazone derivatives. The synthesized quinaxoline derivatives were evaluated for their expected antimicrobial activity; whe...
Source: Medicinal Chemistry Research - October 1, 2018 Category: Chemistry Source Type: research

Synthesis, anti-parasitic activity and QSAR study of a new library of polysubstituted tetrahydronaphtho[1,2- b ]azepines
AbstractA new series of twenty two 2-exo-aryl(heteroaryl)-1,4-epoxytetrahydronaphtho[1,2-b]azepines8–10 and eighteencis-2-aryl(heteroaryl)-4-hydroxytetrahydronaphtho[1,2-b]azepines11–13 were synthesized, and most of them were tested for their ability to inhibit the in vitro growth of the extracellular forms ofTrypanosoma cruzi andLeishmania infantum parasites. Cell toxicity was also determined on Vero and THP-1 mammalian cells. Seventeen compounds exhibited potent activity against the epimastigotes (IC50 lower than 20  µM), without cytotoxicity on Vero cells. Ten compounds also showed remarkable an...
Source: Medicinal Chemistry Research - October 1, 2018 Category: Chemistry Source Type: research

Synthesis, mechanistic and synergy studies of diarylidenecyclohexanone derivatives as new antiplasmodial pharmacophores
AbstractDiarylidenecyclohexanone (DAC) derivatives (Ia-i,IIa-c andIIIa-b) were synthesized, characterized and screened for theirinvitro antiplasmodial activities against erythrocytic stages of chloroquine (CQ) sensitive and resistant strains ofP. falciparum by using SYBR green I fluorescence assay. SAR studies of DAC derivatives showed antiplasmodial activity in the order of 3-NO2 (Ib, IC50 0.95  µM) >  3-chloro (Id, IC50 3  µM) >  4-chloro (Ie, IC50 8.5  µM) >  2-chloro (Ic, IC50 13  µM). FurtherIb andId exhibited nearly...
Source: Medicinal Chemistry Research - October 1, 2018 Category: Chemistry Source Type: research

Intracellular distribution of new tacrine analogues as a potential cause of their cytotoxicity against human neuroblastoma cells SH-SY5Y
AbstractFour new glyco-conjugated tacrine derivatives, 4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-1-(1,2,3,4-tetrahydroacridin-9-yl)thiosemicarbazide (1), 4-(2,3,4,6-tetra-O-acetyl-β-D-mannopyranosyl)-1-(1,2,3,4-tetrahydroacridin-9-yl)thiosemicarbazide (2), 2 ′-(1,2,3,4-tetrahydroacridin-9-yl)hydrazono-3′-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-1 ′,3′-thiazolidin-4′-one (3) and [2 ′-(1,2,3,4-tetrahydro-acridin-9-yl)hydrazono-3′-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-4 ′-oxothiazolidin-5-yliden]acetate (4) were synthesized and their characteri...
Source: Medicinal Chemistry Research - October 1, 2018 Category: Chemistry Source Type: research

Activity evaluation of some psychoactive drugs with the application of QSAR/QSPR modeling methods
AbstractA set of psychoactive drugs has been analyzed with the use of quantitative structure –activity/property relationships methods. The purpose of this study was to demonstrate both the common and differentiating characteristics of the above-mentioned chemical compounds, physicochemical as well as pharmacological based on the quantum chemical calculations and selected biological activi ty data and chromatographic retention parameters. During the study, the ab initio model of molecular modeling was performed and PCA, FA, and MLR as the types of chemometric approach. QSAR/QSPR models were proposed based on chosen st...
Source: Medicinal Chemistry Research - October 1, 2018 Category: Chemistry Source Type: research

Design, synthesis and identification of novel substituted isothiochromene analogs as potential antiviral and cytotoxic agents
In this study, we present the synthesis of novel isothiochromenes, thiazolidonone, thiazinone, arylidines, triazoles, and pyrimidinone compounds based on the starting material 3-amino- isothiochromene-4-carbonitrile3. The chemical structures were confirmed using spectroscopic methods and elemental analyses. These compounds were screened for their in vitro antiviral and antitumor activities. Compounds10a-c and22a-b showed activity against herpes simplex virus-1 (HSV-1) and human immunodeficiency virus-1 (HIV-1). Compounds15 and21a-b exhibited activity against various types of cancer cell lines.Compounds22a-b and10a-c showed...
Source: Medicinal Chemistry Research - October 1, 2018 Category: Chemistry Source Type: research

Synthesis of novel vitamin E containing sulfa drug derivatives and study their antibacterial activity
AbstractA new series of ethoxymethyleneimino sulfa drug (2a–d), alpha-tocopheryl acetamide (5), (N-substituted)sulfamoyl)phenylimino)methyl)alpha-tocopheryl acetamide (6a–d), and (N-substituted)sulfamoyl)phenyl)alpha-tocopheryl acetamide (9a–d) derivatives were synthesized. The newly synthesized compounds were confirmed by spectroscopic tools (IR,1H NMR, and13C NMR, and mass spectra) and evaluated for their antibacterial activities against Gram-positive and Gram-negative bacteria. Gram-negative bacteria,Pseudomonas aeruginosa andSalmonella sp. andEnterococcus italicus showed resistance to all the standard...
Source: Medicinal Chemistry Research - October 1, 2018 Category: Chemistry Source Type: research

Effect of pterostilbene complexed with cyclodextrin on rat liver: potential reduction of oxidative damage and modulation redox-sensitive proteins
The objectives of this study were to promote the aqueous solubility of pterostilbene (PTS) by complexation with hydroxypropyl- β-cyclodextrin (HPβCD), characterize the complex under physical aspects, to make its oral administration feasible in biological tests, and to investigate their pharmacological properties. For 14 days, rats received daily PTS:HPΒCD complex at doses of 25, 50, or 100 mg kg−1 per day orally. The results showed no kidney or liver damage, nor any induction of apoptosis by the administered doses. Also, the complex showed dose-dependent antioxidant effects in the rat liv...
Source: Medicinal Chemistry Research - October 1, 2018 Category: Chemistry Source Type: research

Phytochemical study of Piliostigma thonningii , a medicinal plant grown in Nigeria
AbstractPiliostigma thonningii (Schumach.) Milne-Redhead. (Leguminosae) is used for various medicinal purposes in African countries. Phytochemical investigation ofP. thonningii yielded two compounds newly isolated from natural sources, 2β-methoxyclovan-9α-ol (1), and methyl-ent-3β-hydroxylabd-8(17)-en-15-oate (2), along with 14 known compounds (3–16). Compounds1 and4 (alepterolic acid) showed potential selectivity towardsTrypanosoma brucei brucei with IC50 7.89 and 3.42  μM, respectively. Compound2 showed activity towardsT. brucei andLeishmania donovani Amastigote with IC50 3.84 and 7.82 &th...
Source: Medicinal Chemistry Research - October 1, 2018 Category: Chemistry Source Type: research

Synthesis, antitumor evaluation and molecular docking study of a novel podophyllotoxin-lonidamine hybrid
AbstractA novel podophyllotoxin-lonidamine hybrid was synthesized, and evaluated for its in vitro cytotoxicity by CCK-8 assay. The conjugate,Da, exhibited comparable antiproliferative activity in human normal and multidrug-resistance leukemia cancer cells. Flow cytometry suggested thatDa could induce G2 phase cycle arrest and apoptosis of resistant K562/VCR cells, simultaneously increase the mitochondrial membrane depolarization. Furthermore, immunocytochemistry showed thatDa could significantly disrupt the microtubule organization in K562/VCR cells. Molecular modeling demonstrated thatDa was able to bind into the colchici...
Source: Medicinal Chemistry Research - October 1, 2018 Category: Chemistry Source Type: research

First report of dual cyclooxygenase-2 and 5-lipoxygenase inhibitory halogen derivatives from the thallus of intertidal seaweed Kappaphycus alvarezii
AbstractTwo halogen derivatives, characterized as 2-butyl-7-4-(chloromethyl) cyclooct-1-enyl) hept-5-en-1-ol (compound1) and 4-(2-chloroethyl)-5-7-(methoxymethyl) undec-3-enyl) cyclooct-4-enone (compound2) were isolated from the ethyl acetate-methanol extract of the intertidal red seaweedKappaphycus alvarezii. The studied compounds were evaluated for their inhibitory effects towards pro-inflammatory 5-lipoxygenase along with cyclooxygenases, and also were determined the free radical scavenging potential. The halogenated cyclooctenone (compound2) displayed greater 5-lipoxygenase (IC50 0.90  mg mL−1) inhi...
Source: Medicinal Chemistry Research - October 1, 2018 Category: Chemistry Source Type: research

Effect of Buddleja scordioides K. leaves infusion on lipid peroxidation in mice with ultraviolet light-induced oxidative stress
AbstractThe aim of the study was to evaluate the effect ofBuddleja scordioides Kunth leaves infusion on lipid peroxidation in mice with ultraviolet (UV) light-induced oxidative stress. CD-1 mice were allocated into treatment and control groups (n = 8). Mice in the intervention group were treated withB. scordioides leaves infusion (500  µL equivalent to 0.6534 mg of lyophilized leave infusion/kg of body weight) while the controls received distilled water by gavage administration during 9 days. Both groups were UV irradiated (2.59320175 mW/cm2) 4 consecutive days: 3  h per day ...
Source: Medicinal Chemistry Research - October 1, 2018 Category: Chemistry Source Type: research

Synthesis and trypanocide activity of chloro- l -tyrosine and bromo- l -tyrosine derivatives
AbstractTwenty-two halogenatedl-tyrosine derivatives were synthesized to examine new substances for the treatment of Chagas disease. The synthesis of these derivatives with different degree of substitution in the amino group with methyl iodide, giving primary, tertiary, and quaternary amino acids. All compounds were tested in vitro against intracellular amastigotes ofTrypanosoma cruzi, and the cytotoxicity were evaluated over monocytic cell line U-937. Compound25 was the most active againstT. cruzi with a EC50 of 75.52  µM compared with benznidazole with a EC50 of 58.79  µM. Compounds3,4,7, and15 ...
Source: Medicinal Chemistry Research - September 25, 2018 Category: Chemistry Source Type: research

An unreported polyether macrocyclic lactone with antioxidative and anti-lipoxygenase activities from the Babylonidae gastropod mollusc Babylonia spirata
AbstractA 16-member polyether macrocyclic lactone, with previously unreported framework was isolated as a result of the bioassay guided chromatographic fractionation of the ethyl acetate-methanol extract of the BabylonidaeBabylonia spirata collected from the southwestern coast of Indian peninsular. The compound was characterized as 10, 14-dihydroxy-4-(1 ′-propyl-1′(Z)-hexen-1 ′-yl)-7, 12-dioxapentadecanolide based on extensive spectral data analysis. The antioxidant activities evaluated byin vitro free radical scavenging capacities reported that the studied compound possessed greater activity (IC50 0.058 ...
Source: Medicinal Chemistry Research - September 24, 2018 Category: Chemistry Source Type: research

Synthesis and evaluation of cadiolide analogues as inhibitors of bacterial biofilm formation
AbstractBacterial biofilm infections pose a major clinical challenge due to the ability of biofilms to resist high levels of conventional antibiotics. In the present study, we describe the synthesis and biofilm inhibiting properties of nine new butenolides related to the cadiolide family of marine antibiotics. Eight new cadiolide analogues were synthesized using oxazole −ynone Diels−Alder cycloaddition/cycloreversion as the key step. Their effects on bacterial growth and biofilm formation were investigated against a range of Gram-positive and Gram-negative bacteria, namelyStaphylococcus aureus, Enterococcus fae...
Source: Medicinal Chemistry Research - September 17, 2018 Category: Chemistry Source Type: research

Design, synthesis and biological evaluation of ( E )-3-(3,4,5-trimethoxyphenyl) acrylic acid (TMCA) amide derivatives as anticonvulsant and sedative agents
AbstractIn this article, a novel series of (E)-3-(3,4,5-trimethoxyphenyl)acrylic acid (TMCA) amide derivatives1-18 were designed and synthesized by a facile and one-pot step, which were achieved with good yields using 1-hydroxybenzotriazole (HOBT) and 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) as activation system. All the synthesized derivatives were biologically evaluated for their anticonvulsant, sedative activity and neurotoxicity using the maximal electroshock (MES) model,sc-pentylenetetrazol (PTZ) model, pentobarbital sodium-induced sleeping model, and locomotor activity tests, respectively. A...
Source: Medicinal Chemistry Research - September 15, 2018 Category: Chemistry Source Type: research

Synthesis of chalcones with antiproliferative activity on the SH-SY5Y neuroblastoma cell line: Quantitative Structure –Activity Relationship Models
AbstractChalcones are a group of molecules with a broad spectrum of biological activities, being especially appealing for their antiproliferative effects on several cancer cell lines. For this reason, we synthesized 23 chalcones with good to excellent yields and assessed their effect on the viability of the SH-SY5Y neuroblastoma cell line and on primary human fibroblasts. The results indicated that 18 of these compounds were more active than 5-fluorouracil in the cancer cell line and one of them was more selective than this reference drug. To identify structural features related to the antiproliferative activity of these c...
Source: Medicinal Chemistry Research - September 15, 2018 Category: Chemistry Source Type: research

Design, synthesis and biological evaluation of ( E )-3-(3,4,5-trimethoxyphenyl) acrylic acid (TMCA) amide derivatives as anticonvulsant and sedative agents
AbstractIn this article, a novel series of (E)-3-(3,4,5-trimethoxyphenyl)acrylic acid (TMCA) amide derivatives1-18 were designed and synthesized by a facile and one-pot step, which were achieved with good yields using 1-hydroxybenzotriazole (HOBT) and 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) as activation system. All the synthesized derivatives were biologically evaluated for their anticonvulsant, sedative activity and neurotoxicity using the maximal electroshock (MES) model,sc-pentylenetetrazol (PTZ) model, pentobarbital sodium-induced sleeping model, and locomotor activity tests, respectively. A...
Source: Medicinal Chemistry Research - September 15, 2018 Category: Chemistry Source Type: research

Synthesis of chalcones with antiproliferative activity on the SH-SY5Y neuroblastoma cell line: Quantitative Structure –Activity Relationship Models
AbstractChalcones are a group of molecules with a broad spectrum of biological activities, being especially appealing for their antiproliferative effects on several cancer cell lines. For this reason, we synthesized 23 chalcones with good to excellent yields and assessed their effect on the viability of the SH-SY5Y neuroblastoma cell line and on primary human fibroblasts. The results indicated that 18 of these compounds were more active than 5-fluorouracil in the cancer cell line and one of them was more selective than this reference drug. To identify structural features related to the antiproliferative activity of these c...
Source: Medicinal Chemistry Research - September 15, 2018 Category: Chemistry Source Type: research

Synthesis, cytotoxic activity, and mode of action of new Santacruzamate A analogs
This study demonstrated that synthetic analogs of santacruzamate A with zinc-linked groups are effective for improving both HDAC inhibition and antitumor activity. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - September 14, 2018 Category: Chemistry Source Type: research

Cytotoxicity, apoptosis, and QSAR studies of phenothiazine derived methoxylated chalcones as anticancer drug candidates
AbstractIn the present study, chalcones “(E)-1-(10H-phenothiazine-2-yl)-3-aryl-prop-2-en-1-ones,FS1-11” were successfully synthesized via base-catalyzed Claisen–Schmidt condensation. Chemical structures of the compounds were confirmed by1H NMR,13C NMR, and HRMS techniques. Aryl part of the chalcone was changed as mono, di, and trimethoxylated phenyls. Cytotoxicities of the phenothiazine derivatives were evaluated against four human oral squamous cell carcinoma (OSCC) cell lines (Ca9-22, HSC-2, HSC-3, and HSC-4) and three human normal oral cells (HGF, HPLF, and HPC) by MTT test. The CC50 values of the comp...
Source: Medicinal Chemistry Research - September 8, 2018 Category: Chemistry Source Type: research

Effect of Buddleja scordioides K. leaves infusion on lipid peroxidation in mice with ultraviolet light-induced oxidative stress
AbstractThe aim of the study was to evaluate the effect ofBuddleja scordioides Kunth leaves infusion on lipid peroxidation in mice with ultraviolet (UV) light-induced oxidative stress. CD-1 mice were allocated into treatment and control groups (n = 8). Mice in the intervention group were treated withB. scordioides leaves infusion (500  µL equivalent to 0.6534 mg of lyophilized leave infusion/kg of body weight) while the controls received distilled water by gavage administration during 9 days. Both groups were UV irradiated (2.59320175 mW/cm2) 4 consecutive days: 3  h per day ...
Source: Medicinal Chemistry Research - September 4, 2018 Category: Chemistry Source Type: research

Intracellular distribution of new tacrine analogues as a potential cause of their cytotoxicity against human neuroblastoma cells SH-SY5Y
AbstractFour new glyco-conjugated tacrine derivatives, 4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-1-(1,2,3,4-tetrahydroacridin-9-yl)thiosemicarbazide (1), 4-(2,3,4,6-tetra-O-acetyl-β-D-mannopyranosyl)-1-(1,2,3,4-tetrahydroacridin-9-yl)thiosemicarbazide (2), 2 ′-(1,2,3,4-tetrahydroacridin-9-yl)hydrazono-3′-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-1 ′,3′-thiazolidin-4′-one (3) and [2 ′-(1,2,3,4-tetrahydro-acridin-9-yl)hydrazono-3′-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-4 ′-oxothiazolidin-5-yliden]acetate (4) were synthesized and their characteri...
Source: Medicinal Chemistry Research - September 3, 2018 Category: Chemistry Source Type: research

Synthesis of novel vitamin E containing sulfa drug derivatives and study their antibacterial activity
AbstractA new series of ethoxymethyleneimino sulfa drug (2a–d), alpha-tocopheryl acetamide (5), (N-substituted)sulfamoyl)phenylimino)methyl)alpha-tocopheryl acetamide (6a–d), and (N-substituted)sulfamoyl)phenyl)alpha-tocopheryl acetamide (9a–d) derivatives were synthesized. The newly synthesized compounds were confirmed by spectroscopic tools (IR,1H NMR, and13C NMR, and mass spectra) and evaluated for their antibacterial activities against Gram-positive and Gram-negative bacteria. Gram-negative bacteria,Pseudomonas aeruginosa andSalmonella sp. andEnterococcus italicus showed resistance to all the standard...
Source: Medicinal Chemistry Research - September 3, 2018 Category: Chemistry Source Type: research

Synthesis, mechanistic and synergy studies of diarylidenecyclohexanone derivatives as new antiplasmodial pharmacophores
AbstractDiarylidenecyclohexanone (DAC) derivatives (Ia-i,IIa-c andIIIa-b) were synthesized, characterized and screened for theirinvitro antiplasmodial activities against erythrocytic stages of chloroquine (CQ) sensitive and resistant strains ofP. falciparum by using SYBR green I fluorescence assay. SAR studies of DAC derivatives showed antiplasmodial activity in the order of 3-NO2 (Ib, IC50 0.95  µM) >  3-chloro (Id, IC50 3  µM) >  4-chloro (Ie, IC50 8.5  µM) >  2-chloro (Ic, IC50 13  µM). FurtherIb andId exhibited nearly...
Source: Medicinal Chemistry Research - August 28, 2018 Category: Chemistry Source Type: research

First report of dual cyclooxygenase-2 and 5-lipoxygenase inhibitory halogen derivatives from the thallus of intertidal seaweed Kappaphycus alvarezii
AbstractTwo halogen derivatives, characterized as 2-butyl-7-4-(chloromethyl) cyclooct-1-enyl) hept-5-en-1-ol (compound1) and 4-(2-chloroethyl)-5-7-(methoxymethyl) undec-3-enyl) cyclooct-4-enone (compound2) were isolated from the ethyl acetate-methanol extract of the intertidal red seaweedKappaphycus alvarezii. The studied compounds were evaluated for their inhibitory effects towards pro-inflammatory 5-lipoxygenase along with cyclooxygenases, and also were determined the free radical scavenging potential. The halogenated cyclooctenone (compound2) displayed greater 5-lipoxygenase (IC50 0.90  mg mL−1) inhi...
Source: Medicinal Chemistry Research - August 28, 2018 Category: Chemistry Source Type: research

Phytochemical study of Piliostigma thonningii , a medicinal plant grown in Nigeria
AbstractPiliostigma thonningii (Schumach.) Milne-Redhead. (Leguminosae) is used for various medicinal purposes in African countries. Phytochemical investigation ofP. thonningii yielded two compounds newly isolated from natural sources, 2β-methoxyclovan-9α-ol (1), and methyl-ent-3β-hydroxylabd-8(17)-en-15-oate (2), along with 14 known compounds (3–16). Compounds1 and4 (alepterolic acid) showed potential selectivity towardsTrypanosoma brucei brucei with IC50 7.89 and 3.42  μM, respectively. Compound2 showed activity towardsT. brucei andLeishmania donovani Amastigote with IC50 3.84 and 7.82 &th...
Source: Medicinal Chemistry Research - August 25, 2018 Category: Chemistry Source Type: research

Design, synthesis and identification of novel substituted isothiochromene analogs as potential antiviral and cytotoxic agents
In this study, we present the synthesis of novel isothiochromenes, thiazolidonone, thiazinone, arylidines, triazoles, and pyrimidinone compounds based on the starting material 3-amino- isothiochromene-4-carbonitrile3. The chemical structures were confirmed using spectroscopic methods and elemental analyses. These compounds were screened for their in vitro antiviral and antitumor activities. Compounds10a-c and22a-b showed activity against herpes simplex virus-1 (HSV-1) and human immunodeficiency virus-1 (HIV-1). Compounds15 and21a-b exhibited activity against various types of cancer cell lines.Compounds22a-b and10a-c showed...
Source: Medicinal Chemistry Research - August 24, 2018 Category: Chemistry Source Type: research

Design, synthesis and biological evaluation of quinoxaline N -propionic and O -propionic hydrazide derivatives as antibacterial and antifungal agents
AbstractNovel series of quinaxoline derivatives incorporatingN-propionic andO-propionic hydrazide moieties were synthesized. Alkylation of 3-methylquinoxalin-2(1H)-one with ethyl 2-bromopropanoate afforded a mixture ofO-alkylated andN-alkylated 3-methylquinoxaline. Hydrazide derivatives were afforded by reaction ofO-alkylated andN-alkylated 3-methylquinoxaline with hydrazine hydrate. Condensation of hydrazide derivatives with different aromatic aldehydes and formylpyrazoles afforded the corresponding hydrazone derivatives. The synthesized quinaxoline derivatives were evaluated for their expected antimicrobial activity; whe...
Source: Medicinal Chemistry Research - August 17, 2018 Category: Chemistry Source Type: research

Activity evaluation of some psychoactive drugs with the application of QSAR/QSPR modeling methods
AbstractA set of psychoactive drugs has been analyzed with the use of quantitative structure –activity/property relationships methods. The purpose of this study was to demonstrate both the common and differentiating characteristics of the above-mentioned chemical compounds, physicochemical as well as pharmacological based on the quantum chemical calculations and selected biological activi ty data and chromatographic retention parameters. During the study, the ab initio model of molecular modeling was performed and PCA, FA, and MLR as the types of chemometric approach. QSAR/QSPR models were proposed based on chosen st...
Source: Medicinal Chemistry Research - August 10, 2018 Category: Chemistry Source Type: research

Synthesis, anti-parasitic activity and QSAR study of a new library of polysubstituted tetrahydronaphtho[1,2- b ]azepines
AbstractA new series of twenty two 2-exo-aryl(heteroaryl)-1,4-epoxytetrahydronaphtho[1,2-b]azepines8–10 and eighteencis-2-aryl(heteroaryl)-4-hydroxytetrahydronaphtho[1,2-b]azepines11–13 were synthesized, and most of them were tested for their ability to inhibit the in vitro growth of the extracellular forms ofTrypanosoma cruzi andLeishmania infantum parasites. Cell toxicity was also determined on Vero and THP-1 mammalian cells. Seventeen compounds exhibited potent activity against the epimastigotes (IC50 lower than 20  µM), without cytotoxicity on Vero cells. Ten compounds also showed remarkable an...
Source: Medicinal Chemistry Research - August 9, 2018 Category: Chemistry Source Type: research

Effect of pterostilbene complexed with cyclodextrin on rat liver: potential reduction of oxidative damage and modulation redox-sensitive proteins
The objectives of this study were to promote the aqueous solubility of pterostilbene (PTS) by complexation with hydroxypropyl- β-cyclodextrin (HPβCD), characterize the complex under physical aspects, to make its oral administration feasible in biological tests, and to investigate their pharmacological properties. For 14 days, rats received daily PTS:HPΒCD complex at doses of 25, 50, or 100 mg kg−1 per day orally. The results showed no kidney or liver damage, nor any induction of apoptosis by the administered doses. Also, the complex showed dose-dependent antioxidant effects in the rat liv...
Source: Medicinal Chemistry Research - August 8, 2018 Category: Chemistry Source Type: research

Synthesis, antitumor evaluation and molecular docking study of a novel podophyllotoxin-lonidamine hybrid
AbstractA novel podophyllotoxin-lonidamine hybrid was synthesized, and evaluated for its in vitro cytotoxicity by CCK-8 assay. The conjugate,Da, exhibited comparable antiproliferative activity in human normal and multidrug-resistance leukemia cancer cells. Flow cytometry suggested thatDa could induce G2 phase cycle arrest and apoptosis of resistant K562/VCR cells, simultaneously increase the mitochondrial membrane depolarization. Furthermore, immunocytochemistry showed thatDa could significantly disrupt the microtubule organization in K562/VCR cells. Molecular modeling demonstrated thatDa was able to bind into the colchici...
Source: Medicinal Chemistry Research - August 8, 2018 Category: Chemistry Source Type: research

In vitro leishmanicidal activity of lactone 1,4-dihydroquinoline derivatives against Leishmania (Leishmania) amazonensis
AbstractA series of lactone 1,4-dihydroquinoline derivatives4 (4 and4aa–4cm) was screened for in vitro antileishmanial activity against the promastigote form ofLeishmania (Leishmania) amazonensis. Screening results indicate that all of the synthesized compounds significantly reduced the growth of promastigote forms of promastigotes ofL. (L.) amazonensis. The cytotoxicity of the most active compounds was also measured on peritoneal macrophage cells. Compounds4ah and4bn showed better activities than other derivatives with IC50 values of 6.22 and 9.05  μM, respectively, with selectivity index 22 and 15 times l...
Source: Medicinal Chemistry Research - August 7, 2018 Category: Chemistry Source Type: research

Computational molecular modelling of N -cinnamoyl and hydroxycinnamoyl amides as potential α-glucosidase inhibitors
AbstractIn the present work, a molecular modelling has been performed on a total of 17 cinnamic acids, derived with different amino acids. These have recently been evaluated as potential α-glucosidase inhibitors. Consequently, we proposed a quantitative 3D structure–activity relationships in order to obtain predictive models of the biological activity. Two types of descriptors were used for the modelling: quantum chemical and multi-linear algebraic maps. The first one was obtaine d by using Density Functional Theory (DFT) at the M06/6-311++G(d,p) level, while for the second, attribute sets were obtained by usin...
Source: Medicinal Chemistry Research - August 6, 2018 Category: Chemistry Source Type: research

Development of hydroxamic acid derivatives as anticancer agent with the application of 3D-QSAR, docking and molecular dynamics simulations studies
AbstractThe inhibition of histone deacetylase (HDAC) has become a well-recognized target for cancer therapy. Until now only five HDAC inhibitors i.e., SAHA, romidepsin (FK-228), belinostat, chidamide, and panobinostat have been approved by FDA. The first four of them are being employed for the treatment of cutaneous T-cell lymphoma and last one is being used for the treatment of multiple myeloma. In the present study, structure and ligand-based computational approaches were selected to design novel histone deacetylase inhibitors. A ligand-based pharmacophore model was developed employing phase module that exhibited five si...
Source: Medicinal Chemistry Research - August 4, 2018 Category: Chemistry Source Type: research