Design, synthesis and biological evaluation of aloperine derivatives as potential anticancer agents.

Modifications at different positions on the aloperine molecule were performed to improve its anticancer activity and develop anticancer drugs. The anticancer activities of 44 synthesized compounds were evaluated. The effect of modification positions on anticancer activity was discussed and a structure-activity relationship analysis was established.

Facile synthesis and cytotoxicity of substituted uracil-1'()-acetic acid and 4-pyridone-1'()-acetic acid esters of 20(S)-camptothecins.

A series of novel substituted uracil-1'()-acetic acid esters (-) and 4-pyridone-1'()-acetic acid esters (-) of 20(S)-camptothecins (CPTs) have been synthesized by the acylation method. All of these new esters were assayed for cytotoxicity against five human cancer cell lines A549, Bel7402, BGC-823, HCT-8 and A2780. The bioassay results showed that all the synthesized compounds - had cytotoxities that were higher than TPT and comparable to CPT on these five tumor cell lines, some of them even showed comparable or superior cytotoxic activity to CPT.

Blocking the major inflammatory pathways by newly synthesized thiadiazine derivatives via in-vivo, in-vitro and in-silico mechanism.

A series of new thiadiazine derivatives including 2-(5-alkyl/aryl-6-thioxo-1,3,5-thiadiazinan-3-yl) propanoic acids (a) and 4-methyl-2-(5-alkyl/aryl-6-thioxo-1,3,5-thiadiazinan-3-yl) pentanoic acids (b) were synthesized by reacting primary alkyl/aryl amines with CS, followed by reaction with formaldehyde and amino acids. The chemical structures of synthesized compounds were confirmed by C- NMR and H- NMR techniques. The inhibitory potential of major inflammatory enzymes, COX-2 and 5-LOX was examined.

Synthesis and antiviral activity of lycorine derivatives.

There are no effective antiviral drugs to treat hand, foot, and mouth disease. In this study, a series of lycorine derivatives were synthesized and evaluated against enterovirus 71 and coxsackievirus A16 . Derivatives with the phenoxyacyl group at the C-1 position showed higher efficacy and lower toxicity than lycorine.

LiCl-promoted amination of β-methoxy amides (γ-lactones).

An efficient and mild method has been developed for the amination of β-methoxy amides (γ-lactones) including natural products michelolide, costunolide and parthenolide derivatives by using lithium chloride in good yields. This reaction is applicable to a wide range of substrates with good functional group tolerance. Mechanism studies show that the reactions undergo a LiCl promoted MeOH elimination from the substrates to form the corresponding α,β-unsaturated intermediates followed by the Michael addition of amines.

Synthesis and antitumor activity of novel substituted uracil-1'(N)-acetic acid ester derivatives of 20(S)-camptothecins.

A series of novel substituted uracil-1'(N)-acetic acid esters (6-20) of camptothecins (CPTs) were synthesized by the acylation method. These new compounds were evaluated for in vitro antitumor activity against tumor cell lines, A549, Bel7402, BGC-823, HCT-8 and A2780. In vitro results showed that most of the derivatives exhibited comparable or superior cytotoxicity compare to CPT (1) and topotecan (TPT, 2), with 12 and 13 possessing the best efficacy.

Synthesis and cytotoxicity of novel 20-O-linked homocamptothecin ester derivatives as potent topoisomerase I inhibitors.

In an attempt to improve the antitumor activity of homocamptothecins (hCPTs), a series of novel 20-O-linked hCPT ester derivatives were first designed and synthesized based on a synthetic route, by which hCPTs are acylated with different substituted phenoxyacetic acid ester derivatives. Most of the derivatives were assayed for in vitro cytotoxicity against six human cancer cell lines KB, KB/VCR, A549, HCT-8, Bel7402, and A2780, and most of the assayed compounds exhibited good antiproliferative activity on these tumor cell lines especially on KB.

Synthesis and antiviral activity of phthiobuzone analogues.

A series of phthiobuzone analogs, prepared from potassium phthalimide or phthalandione, have been evaluated for their antiviral activities. Among the candidates, compounds 5j and 5k, which contain the substituted 4-halogenated phenyl ring at N-4',4'' position, show more potent antiviral activity than phthiobuzone against herpes simplex virus 1 (IC(50)=8.56 and 2.

Synthesis and antitumor activity of nitrogen-based thiocolchicine derivatives.

Aim: To search for colchicine derivatives which have high efficacy and low toxicity.

Methods: Colchicine was firstly converted into thiocolchicine, and then it was hydrolyzed to get 7-(N-deacetylthiocolchicine). At last, 7-(N-deacetylthiocolchicine) was amidated to get the target compounds.

Synthesis and antitumor activity of A-ring modified hexacyclic analogues of camptothecin.

Aim: To improve the biological activity of A-ring modified analogues of camptothecin.

Methods: A-ring modified camptothecins were synthesized from 10-hydroxycamptothecin or 7-ethyl-10-hydroxycamptothecin (SN-38) in three or four steps. Their cytotoxicity was evaluated using MTY assay, and their in vivo antitumnor activity against mouse liver cancer H22 was tested.

[Synthesis and antitumor activity of 20-O-linked camptothecin ester derivatives].

Aim: To improve the profile of 20 (S)-camptothecin, a series of 20-O-linked camptothecin phenoxyacetic acid ester derivatives have been designed.

Methods: These derivatives were synthesized by the method of acylation. Their chemical structures were confirmed with 1HNMR, IR, MS, and HRMS.

Synthesis and antitumor activity of 20-O-linked nitrogen-based camptothecin ester derivatives.

A series of nitrogen-based 20S-hydroxyl camptothecin ester derivatives were prepared. 3-Aminopropionate of camptothecin was found more cytotoxic in vitro on several human tumor cell lines than 3-amidopropionate of camptothecin. Ester 16 showed best antitumor activity in vivo and in vitro in all esters we prepared.

Regioselective synthesis and cytotoxicities of camptothecin derivatives modified at the 7-, 10- and 20-positions.

A series of 7-acyloxymethylcamptothecin and 20-O-acyl-7-acyloxymethylcamptothecin derivatives were regioselectively prepared on different solvents. 7-Acyloxymethylcamptothecins possess more efficacy than 20-O-acyl-7-acyloxymethylcamptothecins against six human cancer cell lines in vitro.