Design and Synthesis In Silico Drug-like Prediction and Pharmacological Evaluation of Cyclopolymethylenic Homologous of LASSBio-1514.

Acylhydrazones are still an important framework to the design of new bioactive compounds. As treatment of chronic pain represents a clinical challenge, we decided to modify the structure of LASSBio-1514 (1), previously described as anti-inflammatory and analgesic prototype. Applying the homologation as a strategy for molecular modification, we designed a series of cyclopentyl- (2a-e), cyclobutyl- (3a-e), and cyclopropylacylhydrazones (4a-e) that were synthetized and evaluated in murine models of inflammation and pain. A comparison of their in silico physicochemical and drug-like profile was conducted, as well as their anti-inflammatory and analgesic effect. Compounds 4a (LASSBio-1755) and 4e (LASSBio-1757) displayed excellent in silico drug-like profiles and were identified as new analgesic lead-candidates in acute and chronic model of pain, through oral administration.

Síndrome mão-pé induzida por capecitabina: relato de caso / Capecitabine-induced hand-foot syndrome: a case repor / Síndrome mano-pie inducido por capecitabina: relato de caso

A capecitabina é um agente quimioterápico indicado, dentre outros casos, como monoterapia no câncer de mama metastático. A síndrome mão-pé consiste numa das reações adversas associadas ao seu uso e caracteriza-se por eritema doloroso, edema, disestesia, descamação, bolhas e úlceras nas regiões palmar e plantar. Objetivou-se descrever o caso de uma paciente portadora de carcinoma de mama esquerda com metástase hepática que apresentou síndrome mão-pé decorrente do tratamento com capecitabina. Trata-se de um relato de caso ocorrido num hospital universitário de um estado do nordeste do Brasil em 2016. Foi necessária a suspensão do protocolo antineoplásico utilizado. Observou-se remissão parcial dos sintomas após o uso do gel de Aloe vera para o tratamento das áreas afetadas. Ressalta-se a importância do relato para conhecimento dessa reação adversa, facilitando sua identificação e manejo, para promover melhora da qualidade de vida do paciente oncológico (AU).

Capecitabine is a chemotherapeutic agent indicated, among other things, as monotherapy for metastatic breast cancer. Hand-foot syndrome is one of the adverse effects associated with its use and is characterized by painful erythema, edema, dysesthesia, desquamation, blistering and ulcers in the palms and soles. This study presents a case report on a patient with left-sided breast cancer metastasized to the liver, who suffered from capecitabine-induced hand-foot syndrome. The patient was being treated at a university hospital in a state in the Northeast of Brazil in 2016. Her antineoplastic protocol had to be suspended. After the use of Aloe vera gel to treat the affected areas, there was a partial remission of symptoms.It is important to expand knowledge about this adverse reaction, facilitating its identification and management, in order to improve quality of life in cancer patients (AU).

La capecitabina es un agente quimioterápico indicado, entre otros casos, como monoterapia en cáncer de mama metastático. El síndrome mano-pie consiste en una de las reacciones adversas asociadas a su uso, caracterizada por eritema doloroso, edema, parestesia, descamación, ampollas y úlceras en regiones palmar y plantar. Se objetivó describir el caso de una paciente con carcinoma en mama izquierda, con metástasis hepática presentando síndrome de mano-pie derivado del tratamiento con capecitabina. Relato de caso ocurrido en hospital universitario de estado del Noreste brasileño en 2016. Fue necesaria la suspensión del protocolo antineoplásico utilizado. Se observó remisión parcial de los síntomas luego de uso de gel de Aloe Vera para tratamiento de las áreas afectadas. Se destaca la importancia del relato para conocimiento de esta reacción adversa, permitiendo su identificación y manejo, promoviendo mejora de calidad de vida del paciente oncológico (AU).

Novel orally active analgesic and anti-inflammatory cyclohexyl-N-acylhydrazone derivatives.

The N-acylhydrazone (NAH) moiety is considered a privileged structure, being present in many compounds with diverse pharmacological activities. Among the activities attributed to NAH derivatives anti-inflammatory and analgesic ones are recurrent. As part of a research program aiming at the design of new analgesic and anti-inflammatory lead-candidates, a series of cyclohexyl-N-acylhydrazones 10-26 were structurally designed from molecular modification on the prototype LASSBio-294, representing a new class of cycloalkyl analogues. Compounds 10-26 and their conformationally restricted analogue 9 were synthetized and evaluated as analgesic and anti-inflammatory agents in classical pharmacologic protocols. The cyclohexyl-N-acylhydrazones 10-26 and the cyclohexenyl analogue 9 showed great anti-inflammatory and/or analgesic activities, but compound 13 stood out as a new prototype to treat acute and chronic painful states due to its important analgesic activity in a neuropathic pain model.

Design, synthesis, antinociceptive and anti-inflammatory activities of novel piroxicam analogues.

In this paper we report the design, synthesis, antinociceptive and anti-inflammatory activities of a series of benzothiazine N-acylhydrazones 14a­h, planned by structural modification of piroxicam (1), a non steroidal anti-inflammatory drug. Among the synthesized analogues, compounds 14f (LASSBio-1637) and 14g (LASSBio-1639) were identified as novel antinociceptive and anti-inflammatory prototypes, active by oral administration, acting by a mechanism of action that seems to be different from that of piroxicam, since they were inactive as an inhibitor of cyclooxygenase (COX-1 and COX-2) at concentrations of 10 mM.