Febrifugine derivative antimalarial activity: quantum mechanical predictors / Descritores da atividade antimalarial de derivados de febrifugina obtidos via mecânica qüântica

Plasmodium falciparum resistant strain development has encouraged the search for new antimalarial drugs. Febrifugine is a natural substance with high activity against P. falciparum presenting strong emetic property and liver toxicity, which prevent it from being used as a clinical drug. The search for analogues that could have a better clinical performance is a current topic. We aim to investigate the theoretical electronic structure by means of febrifugine derivative family semi-empirical molecular orbital calculations, seeking the electronic indexes that could help the design of new efficient derivatives. The theoretical results show there is a clustering in well-defined ranges of several electronic indexes of the most selective molecules. The model proposed for achieving high selectivity was tested with success.

O desenvolvimento de linhagens resistentes de Plasmodium falciparum tem encorajado a busca por novas drogas antimalariais. A febrifugina é uma substância natural com alta atividade contra o P. falciparum que apresenta propriedade emética e toxicidade para o fígado tal que não permitem o seu uso clínico. A busca por análogos que possam ter uma performance clínica melhor é um tema de pesquisa atual. Nosso objetivo é investigar a estrutura eletrônica teórica de uma família de derivados da febrifugina empregando cálculos semi-empíricos de orbitais moleculares, procurando por índices eletrônicos que possam ajudar a modelar novos derivados mais eficientes. Os resultados teóricos mostram que para as moléculas mais seletivas existe um agrupamento dos valores de determinados índices em intervalos bem definidos. O modelo proposto para se obter alta seletividade foi testado com sucesso.

Synthesis of some novel phthalazinone, quinazolinone derivatives and screeing antimicrobial activity of selective compounds

4-[1 H-INDOL-3-YL]-1H-2, 3-benzoxazin-1-one [1] aminolysis with some sulfa drugs and 4-amino-acetophenone to give the corresponding sulfonamide and acetyl phenyl derivatives 2a-c and 3, The key intermediate compound 3 condensed with aromatic aldehyde to yield alpha, beta-unsaturated keto compound 4a, b. Compound 1 reacted with sodium azide to give the tetrazol derivative 5. Benzoxazinone derivative 6 was obtained via the interaction of compound 2 with anthranilic acid, which in turn was condensed with hydrazine hydrate, hydroxyl amine hydrochloride/formamide and glutamic acid to yield quinazolinone derivatives 7, 8, 9 and pentandioic acid derivative 10, respectively. Compound 7 reacted with aromatic aldehyde to achieve the Schiff's bases 11a, b, c. Compound [11c] reacted with thioglycolic acid to give thiazole derivative 12. On the other hand, compound 7 reacted with acetic anhdride to give diacetyl derivative 13. Some of the prepared compounds were screened for their antimicrobial activity

Design and synthesis of certain imidazo[1,5-a] quinazolin-5 [4H]-ones of anticipated anticonvulsant activity

1 -[alkyl/aryl] - 3 - [1 - [4' -chlorophenyl] - 5 [4H] - oxo - imidazo [l,5-a]quinazolin-4-yl] thiourea 5 derivatives were synthesized from 4-amino-1-[4'-chlorophenyl] imidazo [1,5-a] quinazolin-5[4H]-one 4 which were cyclized into the corresponding thioxoimidazolidindiones 6, thiazolidinones 7 and 8, or 2,3-dihydrothiazol-4-ol 9. Also, some derivatives 10 were synthesized through the reaction of 4 with 5[4H]-oxazolone derivatives. Furthermore, 2-chloro-N-[l -[4'-chlorophenyl]-5[4H]-oxoimidazo[1,5-a] quinazolin-4-yl]acetamide 11 was reacted with sodium valproate or potassium 2-or 4-[3-substituted phenyl or cyclohexyl ureido]benzoate derivatives to give 12 or 13, respectively. Molecular modeling study was achieved to reveal the anticonvulsant activity of the newly synthesized derivatives postulating a hypothesis based on the specific binding with benzodiazepine receptor. Representative examples were chosen and screened for their anticonvulsant activity

Synthesis of some new substituted quinazoline derivatives and their antimicrobial screening

A new series of 4-oxo-6-iodo-3H-quinazoline and its fused heterocyclic analogs were prepared and screened for their antimicrobial activity. Compounds 13, 19, 22, 28 and 32 showed remarkable broad spectrum antimicrobial activity. The fused heterocycles l,2,4-triazino[3,4-c] quinazoline, l,2,4-triazolo[2,3-c]quinazoline and pyrazolo [l,5-c] quinazoline proved to contribute for activity. The detailed synthesis and their antimicrobial screening are reported

Synthesis and anti-HIV activity of some non-nucleoside 2,3-disubstituted quinazoline derivatives (Part-V).

Several [2-phenyl-4(3H)-oxo-3-quinazolinylamino]-N-substituted- arylacetamides (1a-j) have been synthesized and tested at the National Cancer Institute, Bethesda, Maryland, USA, for their anti-HIV activity against susceptible human host cells (CEM cell line) over a wide range of concentrations (6.35 x 10(-8) to 2.00 x 10(-4) M). The highest protection observed is 45.67%. The structures of these compounds have been established on the basis of elemental analysis and spectral data.

Fused pyrimidines synthesis and anti-inflammatory testing of certainnovel imidazo [1,2-c] quinazoline, pyrimido [2,1-a] phthalazine derivatives

A number of heterocyclic compounds containing pyrimidine nucleus, namely, imidazo[l,2-c]quinazolines, pyrazolo[3,4-d]triazoIo[3.4-b]pyrimidines and pyrimido[2,1-a] phthalazines has been synthesized. Acidic moieties that characterize most of nonsteroidal antiinflammatory drugs [NSAIDs] or ester groups, as potential pro-drug functionaIities, have been incorporated. The potency of eight compounds to inhibit carrageenin-induced paw edema in rats has been evaluated

Synthesis and reactions of 2-chloromethyl-6-iodo-3, 1-benzoxazin-4-one with amines

Certain quinazolinones were reported to exert antimicrobial activity[1]. Consequently, in continuation of our previous work on the reaction of 3,1-benzoxazin-4-ones with amines,[2-5], 2-chloromethyl-6- iodobenzoxazin-4-one was synthesized and allowed to react with amines hoping to obtain 4-quinazolinones for evaluation as antimicrobial agents. 5-Iodoanthranilic acid was chloroacetylated to give I which was cyclodehydrated to yield the corresponding 3,1-benzoxazin-4- one II Compound II was allowed to react with different aromatic amines to produce 3-aryl-2-chloromethyl-6-iodoquinazolin-4-ones IIIa-t. Structures of compounds III [Scheme 1] were confirmed by microanalytical and spectroscopic data [Table1 and 2]

Anti-inflammatory and diuretic activity of a new class of compounds--Schiff bases of 3-amino-2-methylquinazolin 4(3H)-ones.

Eighteen Schiff Bases of 3-amino-2-methylquinazolin-4(3H)-ones were synthesised and screened for anti-inflammatory and diuretic activity. Anti-inflammatory activity was identified in PNG-1, PNG-13, PNG-14, PNG-15 and PNG-17.

Non-steriodal anti-inflammatory agents: III-synthesis of pyrazole derivatives of 4 [3H] -quinazolinones

Several groups of compounds were synthesized having a pyrazole or pyrazoline moiety attached to 4[3H]-quinazolinone at the 2- or 3-position either directly or through different linkages. The linkages include methinamino, therapy iminomethyl, aminoethyl or methinehydrazino grouping. The anti-inflammatory activity of representative examples of the products is reported

4 [3H] - quinazolinone derivatives as beta adrenergic blockers

B-aryl-s-triazoline-5-thiones reacted with alpha-haloketones to give the S-substituted derivatives 2, which were cyclized to substituted thiazolo [3,2-b]-s-triazoles 3 and 4. 2-[3-Aryl-2-propenoyl]-3-methyl-6-pheny!-thiazoIo [3,2-b]-s-triazoles [6] were prepared and their behaviour toward amine derivatives and benzanilide were investigated. The structure of the products were elucidated by chemical and physical routes