Synthesis of indazol‐4,7‐dione derivatives as potential trypanocidal agents

The synthesis of new indazol‐4,7‐dione derivatives via 1,3‐dipolar cycloaddition of diazomethane with 2,3‐dimethyl‐1,4‐benzoquinone ( 2 ) and 1,4‐naphthoquinone ( 7 ) followed by N‐alkylation of the pyrazol nitrogen atom of the corresponding quinones ( 3 ) and ( 8 ) with methyl chloroacetate is described. A series of amides from esters ( 5 ) and ( 10 ) were also obtained. These compounds were tested in vitro as potential anti‐trypanosomal agents. Compounds ( 4 ) and ( 8 ) were found to have significant activity.     

Synthesis of 2-thiobenzimidazole derivatives as potential antifilarial agents

Several 5-benzoyl-2-thiobenzimidazole and 2-thiobenzimidazole aliphatic acids, esters, and N,N-dialkyl-carboxamides and thiocarboxamides were prepared by reacting bromo aliphatic acids, bromo aliphatic esters, and N,N-dialkylcarbamoyl or thiocarbamoyl chlorides with 5-benzoyl-2-thiobenzimidazole or 2-thiobenzimidazole in the presence of base. 2-Thiocarbomethoxy- and 2-thiocarboethoxybenzimidazole were prepared by the reaction of 2-thiobenzimidazole with methyl or ethyl chloroformate in the presence of base. However, the reaction of 5-benzoyl-2-thiobenzimidazole with ethyl chloroformate, afforded 5-benzoyl-2-ethylthiobenz-imidazole.     

Synthesis of benzimidazole derivatives as potential H1-antihistaminic agents

Several types of benzimidazole derivatives were prepared and were screened for H ₁-antihistaminic activity. Most of the compounds showed potent antihistaminic activity in vitro. Among them 2-[(1-piperazinyl)methyl]-benzimidazoles 14 and 2-[(1-homopiperazinyi)methyl]benzimidazoles 15 exhibited potent activity also in vivo.     

Synthesis of new boswellic acid derivatives as potential antiproliferative agents

Abstract

In the current investigation, a series of heterocyclic derivatives of boswellic acids were prepared along with new monomers of 3-O-acetyl-11-keto-β-boswellic acid (AKBA, 1) 11-keto-β-boswellic acid (KBA, 2) and several new bis-AKBA and KBA homodimers and AKBA-KBA heterodimers. The effects of these compounds on the proliferation of different human cancer cell lines, viz., FaDu (pharynx carcinoma), A2780 (ovarian carcinoma), HT29 (colon adenocarcinoma), and A375 (malignant melanoma), have been evaluated. Thus, KBA homodimer 21 effectively inhibited the growth of FaDu, A2780, HT29, and A375 cells with EC₅₀ values below 9?μM. In addition, compounds 7, 8, 11, 12, 15, 16, and 17 also exhibited cytotoxic effects for A2780, HT29, and A375 cancer cells. In particular, the pyrazine analog 8 was highly cytotoxic for A375 cancer cells with an EC₅₀ value of 2.1?μM.     

Synthesis of certain tricyclic quinoline derivatives as potential antiamebal agents

Synthesis of the fused tricyclic systems, 1, 2, 3, 3a, 4, 5-hexahydropyrrolo[1, 2a]quinoline (I) and 2, 3, 4, 4a, 5, 6-hexahydro 1H-benzo[c]quinolizine (II), each bearing an ethoxyl substituent on the benzene ring, has been achieved. The compounds combine certain structural features of the alkaloid emetine and of 8-quinolinols.     

Synthesis of 1,2,3,4-tetrahydroquinazoline derivatives as potential alpha-adrenergic blocking agents

The synthesis of N,N′-bis[6-(1,2,3,4-tetrahydro-3-quinazolidyl)hexyl]cystamine (I) and 3-(6-aminohexyl)-1,2,3,4-tetrahydroquinazoline (II) are described. Compound I is obtained by condensation of o-nitrobenzoyl chloride with 3-(6-aminohexyl)-1,3-thiazolidine (III) followed by dimerization, reduction and formation of tetrahydroquinazoline ring. A similar method was used for preparation of compound II. These compounds and some synthesis intermediates are potential alpha-adrenergic blockers.     

Synthesis and biological evaluation of dihydrotriazine derivatives as potential antibacterial agents

A series of 1,4-dihydro-1,3,5-triazine derivatives were designed and synthesized and their antibacterial and antifungal activities were evaluated. Most of the synthesized compounds showed potent inhibition of several Gram-positive bacterial strains(including multidrug-resistant clinical isolates) and Gramnegative bacterial strains, with minimum inhibitory concentrations(MICs) in the range of 2.1–181.2 mmol/L. Compounds 7a and 7c presented the most potent inhibitory activities against Grampositive bacteria(e.g., Staphylococcus aureus 4220), Gram-negative bacteria(e.g., Escherichia coli 1924),and the fungus Candida albicans 7535, with MICs of 2.1 or 4.1 mmol/L. Especially, compound 7a was the most potent, with an MIC of 2.1 mmol/L against four multidrug-resistant, Gram-positive bacterial strains.The cytotoxic activity of the compound 7a, 7c and 7f was assessed in HepG2 cells, and the results suggest that 1,4-dihydro-1,3,5-triazine derivatives bearing a 6-benzyloxynaphthalen moiety are interesting scaffolds for the development of novel antibacterial agents.     

Synthesis and biological evaluation of novel acenaphthene derivatives as potential antitumor agents

Twelve novel acenaphthene derivatives have been synthesized. The structures of all compounds were confirmed by 1H-NMR, MS and elemental analysis. Their antitumor activities were evaluated in six human solid tumor cell lines, namely non-small cell lung cancer (H460), human colon adenocarcinoma (SW480), human breast cancer cell (MDA-MB-468 and SKRB-3), human melanoma cell (A375) and human pancreatic cancer (BxPC-3). Among them, compound 3c shows the best antitumor activity against SKRB-3 cell line, as high as the positive control adriamycin.     

Synthesis of novel spin-labelled combretastatin A-4 derivatives as potential antineoplastic agents

Four novel spin-labelled combretastatin A-4 (CA-4) analogues were first synthesised in quantitative yield by reacting CA-4 with the corresponding nitroxyl radical. Their cytotoxic activities against A-549 (human lung cancer) and HePG-2 (human liver cancer) in?vitro were evaluated, and the results indicated that these derivatives were more cytotoxic than the clinical drug irinotecan.     

Synthesis of 1,3,5-cis,cis-triaminocyclohexane N-pyridyl derivatives as potential antitumor agents

Iron deprivation has been previously proven to be a promising strategy in treating tumor cells. A series of cis,cis-1,3,5-triaminocyclohexane N-pyridyl derivatives as iron-depleting antitumor agents were prepared. Cytotoxic activity of these derivatives was evaluated in the HeLa cancer cell line. Among the tested derivatives, N-ethyl-N,N',N"-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane (17) exhibited potent cytotoxicity against this cancer cell line. On the basis of the structure of 17, a bifunctional iron chelator 24 was designed and prepared. Bifunctional agent 24 possessing a maleimide linker that is functional for conjugation to thiolated monoclonal antibodies is a promising lead compound for development of antitumor conjugates for antibody-targeted therapies.     

4'-Acetamidochalcone derivatives as potential antinociceptive agents

Nine acetamidochalcones were synthesized and evaluated as antinociceptive agents using the mice writhing test. Given intraperitoneally all the compounds were more effective than the two reference analgesic drugs (acetylsalicylic acid and acetaminophen) used for comparison. N-{4-[(2E)-3-(4-nitrophenyl)prop-2-enoyl]phenyl}acetamide (6) was the most effective compound and was therefore selected for more detailed studies. It caused dose-related inhibition in the writhing test, being about 32 to 34-fold more potent than the standard drugs. It was also effective in the second phase of the formalin test and the capsaicin test. These acetamidochalcones, especially compound 6, might be further used as models to obtain new and more potent analgesic drugs.     

Synthesis and NMR elucidation of novel penta-cycloundecane amine derivatives as potential antituberculosis agents

The synthesis and NMR elucidation of five novel penta-cycloundecane amine derivatives are reported. These compounds are potential antituberculosis agents. The (1)H and (13)C spectra showed major overlapping of methine signals of the cage skeleton making it extremely difficult to elucidate these compounds. The overlapping occurs as a result of the additions made to the carbonyl carbon (C-8/C-11) of the cage. The two-dimensional NMR technique proved to be a useful tool in overcoming this problem. All compounds reported are meso compounds thereby not only simplifying the NMR structure elucidation, but also making it indeed possible.     

Synthesis of second-generation sansalvamide A derivatives: novel templates as potential antitumor agents

We report the synthesis of 34 second-generation Sansalvamide A derivatives. San A derivatives have unique anticancer properties and target multiple cancers, including colon, pancreatic, breast, prostate, and melanoma. As novel templates, the derivatives described herein explore the role of stereochemistry, amide bond geometry, transannular hydrogen bonding, and polarity on antitumor potency. Testing the chemotherapeutic activity of these derivatives against multiple cancer cell lines will provide clear structural motifs and identify conformational space that is important for cytotoxicity. The 34 compounds presented are divided into six series, where five series involve the insertion of D-amino acids in conjunction with four structural features at each of the five positions of the macrocycle. The sixth series involves comparison between all L- and all D-amino acid derivatives with N-methyls placed at each position around the macrocyclic core. The four structural features explored in conjunction with D-amino acids include N-methyl amino acids, aromatic amino acids, polar amino acids, and hydrophobic alkyl amino acids.     

Synthesis and in vitro studies of Gd-DTPA derivatives as new potential MRI contrast agents

A new type of dendritic molecules, Gd-DTPA derivatives, which work as a functionalized ligand coordinating gadolinium(III) ion at the center of their frameworks with different terminal moieties on the molecular surfaces, was readily synthesized with high yield. The structures were established by ¹H, ¹³C NMR, and mass spectral studies. In vitro studies showed them to have enhanced r₁ value in albumin medium and good potentiality as MRI contrast agent.     

Synthesis and biological evaluation of novel benzothiazole-2-thiol derivatives as potential anticancer agents

A series of novel benzothiazole-2-thiol derivatives were synthesized and their structures determined by 1H-NMR, 13C-NMR and HRMS (ESI). The effects of all compounds on a panel of different types of human cancer cell lines were investigated. Among them, pyridinyl-2-amine linked benzothiazole-2-thiol compounds 7d, 7e, 7f and 7i exhibited potent and broad-spectrum inhibitory activities. Compound 7e displayed the most potent anticancer activity on SKRB-3 (IC(50) = 1.2 nM), SW620 (IC(50) = 4.3 nM), A549 (IC(50) = 44 nM) and HepG2 (IC(50) = 48 nM) and was found to induce apoptosis in HepG2 cancer cells.     

Synthesis of 3'-beta-carbamoylmethylcytidine (CAMC) and its derivatives as potential antitumor agents

3'-beta-Carbamoylmethylcytidine (CAMC) and its derivatives were synthesized using an intramolecular Reformatsky-type reaction promoted by SmI2 as the key step. In vitro tumor cell growth inhibitory activity was evaluated and CAMC was found to exhibit potent cytotoxicity against various human tumor cell lines. From a structure-activity relationship study it was postulated that the cytotoxic mechanism of action of CAMC did not require phosphorylation at the 5'-hydroxyl group. This study provides a novel strategy for the development of a new type of antitumor nucleoside.     

Synthesis and characterization of some vanadyl complexes with flavonoid derivatives as potential insulin-mimetic agents

Two new complexes with formula VOL₂·nH₂O ((1) L: 4′,5,7-trihydroxyflavone-7-rhamnoglucoside (naringin), n = 8; (2) L: 3′,4′,7-tris[O-(2-hydroxyethyl)]rutin (troxerutin), n = 0) were synthesised and characterised. The IR and UV–Vis spectral data indicate that these flavones act as bidentate chelating ligands and generate VO(II) complexes with a square-pyramidal stereochemistry. The thermal analysis (TG, DTA) elucidated the composition and also the number and nature of the water molecules. The thermal behavior indicates also a strong interaction between oxovanadium (IV) and these oxygen donor ligands.     

Synthesis and biological activities of thio-triazole derivatives as novel potential antibacterial and antifungal agents

A series of novel thio-triazole derivatives including thiols, thioethers and thiones as well as some corresponding triazolium compounds were conveniently and efficiently synthesized from commercially available halobenzyl halides and thiosemicarbazide. All the new compounds were characterized by 1 H NMR, 13 C NMR, FTIR, MS and HRMS spectra. Their antibacterial and antifungal activities in vitro were evaluated against four Gram-positive bacteria, four Gram-negative bacteria and two fungi by two-fold serial dilution technique. The preliminary bioassay indicated that some prepared triazoles exhibited effective antibacterial and antifungal activities. Especially, 3,4-dichlorobenzyl triazolethione and its triazolium derivatives displayed the most potent activities against all the tested strains.     

Synthesis, structural and biological characterization of 5-phenylhydantoin derivatives as potential anticonvulsant agents

Abstract  

Considering the importance of hydantoin derivatives in treatment of status epilepticus, four 5-phenylhydantoins, whose lipophilicities were estimated to be similar to that of phenytoin, were synthesized. Evaluation of their anticonvulsant activities was performed on rats by subcutaneous pentylenetetrazol seizure test and intravenous pentylenetetrazol threshold test, and spontaneous locomotor activity test was used to assess possible sedative effects. X-ray analysis of three compounds suggested that certain analogies might be drawn between interactions in crystal packing and biological interactions responsible for their anticonvulsant activity. It was found that 5-ethyl-5-phenyl-3-propylhydantoin exhibits the most favorable pharmacological properties among the synthesized compounds, i.e., anticonvulsant activity comparable to phenytoin with lower liability for induction of sedation in rats.