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This study describes a virtual screening performed for two series of selenides (28 compounds), derived from N-phenylacetamides chlorides and 7-chloro-quinoline, to determine their potential for leishmanicidal activity against Leishmania amazonensis and Leishmania donovani. Seven compounds were predicted as potential leishmanicides; therefore, they were synthesized from elemental selenium, as a precursor for the production of NaHSe, and subsequent reactions with 4,7-dichloro-quinoline and N-phenylacetamides chlorides were performed. The compounds were characterized by infrared (IR), 1H and 13C nuclear magnetic resonance (NMR), and sent for in vitro cytotoxicity tests against L. amazonensis and were found to be active and selective, and two compounds presented half-maximal inhibitory concentrations (IC50) of 5.67 and 10.81 μg mL-1. They also presented good interaction energies in the docking study, suggesting that may exert their effects by inhibiting the N-myristoyltransferase and O-acetylserine sulfhydrylase enzymes in parasites.

A series of 2,4-diarylaminopyrimidine derivatives bearing hydrophilic hydroxamic acids were designed and synthesized as potent EGFRT790M/L858R inhibitors. Among the derivatives synthesized, 10c (IC50 = 5.192 nM), 10j (IC50 = 10.35 nM), and 10o (IC50 = 0.3524 nM) exhibited higher potencies against EGFRT790/M/L858R compared to the known EGFR inhibitor AZD-9291 (IC50 = 20.80 nM). Moreover, 10j showed moderate activity against H1975 cells transfected with the EGFRT790M/L858R mutant, with an IC50 of 0.2113 μM over A431 (wild-type EGFR, SI = 47.3). In addition, 10j exhibited low toxicity in normal HBE cells (human bronchial epithelial cells, IC50 > 40 μΜ). Analysis of the mode of action indicated that 10j effectively induced apoptosis in H1975 cells by arresting the cells in the G2/M phase. Compound 10j also demonstrated efficacy in inhibiting tumor growth in a H1975 xenograft mouse model without losing body weight or killing the mice. Taken together, these results suggested that 10j might be a promising candidate for development as a potential treatment for NSCLC harboring the EGFRT790M/L858R mutation.

A series of 5-(N-substituted carboxamidoethylthio)-3-(3'pyridyl)-4- amino-1,2,4-triazole derivatives 6a-j have been synthesized and evaluated for anti-tubercular activity. They are screened in-vitro at 10μg/mL concentration against Mycobacterium tuberculosis H37RV (ATCC 27294). All the compounds are showing antitubercular activity when compared with the standard drug Amikacin. Compounds 6e and 6h are found active as they displayed IC50 and IC90 values at 100μg/mL.

A series of new, water-soluble phenyl N-mustard-benzenealkylamide conjugates containing hydrophilic ω-dialkylaminoalkylamide or ω-cyclic aminoalkylamide moieties were synthesized via a bioisostere approach. These compounds have a broad spectrum of antitumor activity against a panel of human tumor cell lines. Of these derivatives, compound 18b effectively suppressed the growth of colon cancer (HCT-116), prostate cancer (PC3), and lung cancer (H460) xenografts. The growth of HCT-116 xenografts was almost completely suppressed when co-treated with compound 18b and 5-fluorouracil. Furthermore, compound 18b can induce DNA cross-linking and cell-cycle arrest at the G2/M phase. Early preclinical studies, including pharmacokinetics in rats, inhibition of the hERG, and 14 days of acute intravenous injection toxicity, suggest that compound 18b is a promising candidate for further preclinical studies.

Background Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder that is characterized by dementia, cognitive impairment, and memory loss. Diverse factors are related to the development of AD, such as increased level of β-amyloid (Aβ), acetylcholine, metal ion deregulation, hyperphosphorylated tau protein, and oxidative stress. Methods The following methods were used: organic syntheses of 1H-phenanthro[9,10-d] imidazole derivatives, inhibition of self-mediated and metal-induced Aβ1-42 aggregation, inhibition studies for acetylcholinesterase and butyrylcholinesterase, anti-oxidation activity studies, CD, MTT assay, transmission electron microscopy, dot plot assay, gel electrophoresis, Western blot, and molecular docking studies. Results We synthesized and characterized a new type of 1H-phenanthro[9,10-d]imidazole derivatives as multifunctional agents for AD treatment. Our results showed that most of these derivatives exhibited strong Aβ aggregation inhibitory activity. Compound 9g had 74% Aβ1-42 aggregation inhibitory effect at 10 μM concentration with its IC50 value of 6.5 μM for self-induced Aβ1-42 aggregation. This compound also showed good inhibition of metal-mediated (Cu2 + and Fe2 +) and acetylcholinesterase-induced Aβ1-42 aggregation, as indicated by using thioflavin T assay, transmission electron microscopy, gel electrophoresis, and Western blot. Besides, compound 9g exhibited cholinesterase inhibitory activity, with its IC50 values of 0.86 μM and 0.51 μM for acetylcholinesterase and butyrylcholinesterase, respectively. In addition, compound 9g showed good anti-oxidation effect with oxygen radical absorbance capacity (ORAC) value of 2.29. Conclusions Compound 9g was found to be a potent multi-target-directed agent for Alzheimer's disease. General significance Compound 9g could become a lead compound for further development as a multi-target-directed agent for AD treatment.

3-Mercapto-(4H)-1,2,4-triazole has been synthesized from 1-formylthiosemicarbazide. Different N-substituted β-chloropropionamides have been prepared by reacting substituted amines with β- chloropropionylchloride. Different Nsubstituted β-chloropropionamides have been condensed with 3-mercapto-(4H)-1,2,4-triazole in basic medium to obtain various 3-(N-substituted carboxamidoethylthio)-(4H)-1,2,4-triazoles. The structure of the synthesized compounds are confirmed by IR, 1H NMR spectra and elemental analysis. All the compounds have been screened for their analgesic, anti-inflammatory and anxiolytic activity.

A series of 4,5-di-substituted acridones have been designed and synthesized. Several compounds show high affinity for telomeric G-quadruplex DNA in classical and competition FRET assays, together with low duplex DNA affinity, although they do not show activity in a telomerase assay or evidence of telomere shortening. They have low toxicity against a panel of cancer cell lines and a normal human fibroblast line, and produce potent senescence-based long-term growth arrest in the MCF7 and A549 cancer cell lines.

The design and synthesis of a series of urea-based nonpolycyclic aromatic ligands with alkylaminoanilino side chains as telomeric and genomic G-quadruplex DNA interacting agents are described. Their interactions with quadruplexes have been examined by means of fluorescent resonance energy transfer melting, circular dichroism, and surface plasmon resonance-based assays. These validate the design concept for such urea-based ligands and also show that they have significant selectivity over duplex DNA, as well as for particular G-quadruplexes. The ligand-quadruplex complexes were investigated by computational molecular modeling, providing further information on structure-activity relationships. Preliminary biological studies using short-term cell growth inhibition assays show that some of the ligands have cancer cell selectivity, although they appear to have low potency for intracellular telomeric G-quadruplex structures, suggesting that their cellular targets may be other, possibly oncogene-related quadruplexes.

The invention concerns compounds of Formula (I) or a salt, solvate or pro-drug thereof. The compounds may be used in therapy, particularly anti-cancer therapy.

The invention provides compounds of formula (I): wherein Ar1 is a monocyclic aryl or heteroaryl; X and Y are each independe ntly a group of formula (II): Z is absent, a group of formula (II), optionally substituted C1-7 alkyl, optionally substituted C3-20 heterocyclyl, optionally substituted C5-20 aryl, halo, amino, hydroxy, ether, thio, thioet her, carboxy or cyano; L1 and L2 are each independently selected from NR 3, C2H2, CH2, -O-, -S- and a bond; Ar2 and Ar3 are independently optionally substituted C 5 or C6 aryl or heteroaryl; n is an integer from 1 to 5; R1 and R2 are independently hydrog en, C1-7 alkyl, C3-20 heterocyclyl, or C 5-20 aryl, or R1 and R2, taken together with the nitrogen atom to which they are attached, form a heterocyclic ring having from 3 to 8 ring atoms; R3 is H or C 1-7 alkyl; and provided that at least one of Ar 1, Ar2 and Ar3 is oxazole, triazole or tetrazole. These compounds are thought to bind G -quadruplexes formed in human telomeres and are therefore useful in anti -cancer therapy. The invention also provides pharmaceutical compositions comprising the novel compounds, and methods for their manufacture.

A series of diarylurea ligands were designed to interact selectively with G-quadruplexes and were synthesised using copper(I) catalysed 'click' chemistry to incorporate the 1,4-substituted 1,2,3-triazole ring into the core of the ligands; the optimal ligands demonstrate a high degree of selective telomeric G-quadruplex stabilisation and are not cytotoxic in several cancer cell lines. The Royal Society of Chemistry.

A series of novel arylcarbamoylalkyltriphenylphosphonium chlorides were synthesized. The newly synthesized compounds, [R-(p-C6H 4)-NH-CO-R1P⊕(C6H 4)3]Clθ, R = H (2), CH3 (4), NO2 (6), R1 = -CH2- (b), CH3CH2CH2- (c), -CH2CH2CH 2 (d), the analogs of an anticancer drug, were characterized by infrared (IR), 1H nuclear magnetic resonance (NMR), 13C-NMR, 31P-NMR, mass spectrometry (MS), thermogravimetry (TG), and conductivity measurements. The anticancer activities of the obtained compounds were measured by MTT. The preliminary results indicated that some compounds showed potent anticancer activities against HCT-8, Bel-7402, A549, and S180.

A compound of formula (I): compositions and medicaments containing the same as well as processes for the preparation and use of such compounds, compositions and medicaments, particularly in diseases associated with inappropriate Aurora activity.

A series of G-quadruplex stabilizing compounds have been prepared via click chemistry employing the Cu(I)-catalyzed Huisgen reaction. These compounds were shown to bind tightly to G-quadruplex DNA even in the presence of competing high concentrations of duplex DNA. Furthermore, a modified TRAP assay has shown that some of these compounds also inhibit telomerase at low micromolar concentration. Copyright

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