Sachin Kumar Sharma

Uma s rie de 11 an logos da curcumina foi submetida a previs o de propriedades moleculares e semelhan a com medicamentos pelos softwares Molinspiration e MolSoft, par metros de lipofilia e solubilidade usando o programa ALOGPS 2.1. Os compostos seguiram a Regra dos cinco de Lipinski e foram sintetizados para triagem anti-HIV como f rmacos/chumbo biodispon veis por via oral. Al m disso, a estrutura dos compostos sintetizados foi confirmada por an lises espectrais (IR, NMR e massa) e os compostos (3a-k) foram avaliados quanto atividade anti-HIV de acordo com o protocolo padr o. A pontua o m xima do modelo de semelhan a com f rmacos (1.1.0) foi encontrada para 3,5-bis(4-hidroxi-3-metilestiril)-N-(4-clorofenil)-1H-pirazol-1-carboxamida (3b). Verificou-se que o composto 3b tinha atividade anti-HIV com IC50 >3,71 M e CC50 3,71 M, no entanto, a atividade foi considerada inferior do medicamento padr o zidovudina.

Seria 11 analog w kurkuminy zostala poddana prognozowaniu wlaściwości molekularnych i podobieństwa do lek w za pomocą oprogramowania Molinspiration i MolSoft, a także parametr w lipofilowości i rozpuszczalności za pomocą programu ALOGPS 2.1. Związki zgodne z "zasadą pięciu" Lipinskiego zostaly zsyntetyzowane w celu przeprowadzenia badań przesiewowych pod kątem dzialania przeciw HIV jako leki/związki wiodące dostępne w postaci doustnej. Następnie struktura zsyntetyzowanych związk w zostala potwierdzona analizami spektralnymi (IR, NMR i masowymi), a związki (3a-k) zostaly ocenione pod kątem dzialania przeciw HIV zgodnie ze standardowym protokolem. Maksymalny wynik modelu podobieństwa do leku (1.1.0) uzyskano dla 3,5-bis(4-hydroksy-3-metylostyrylo)-N-(4-chlorofenylo)-1H-pirazol-1-karboksamidu (3b). Stwierdzono, że związek 3b wykazuje aktywnośc przeciwko HIV z IC50 >3,71 M i CC50 3,71 M, jednak aktywnośc ta byla mniejsza niż w przypadku standardowego leku zydowudyny.

Una serie di 11 analoghi della curcumina stata sottoposta a previsione delle propriet molecolari e somiglianza farmacologica mediante i software Molinspiration e MolSoft, nonch a parametri di lipofilia e solubilit utilizzando il programma ALOGPS 2.1. I composti che seguivano la "Regola dei cinque" di Lipinski sono stati sintetizzati per lo screening anti-HIV come farmaci/principi attivi biodisponibili per via orale. Successivamente, la struttura dei composti sintetizzati stata confermata da analisi spettrali (IR, NMR e massa) e i composti (3a-k) sono stati valutati per l'attivit anti-HIV secondo il protocollo standard. Il punteggio massimo del modello di somiglianza farmacologica (1.1.0) stato riscontrato per il 3,5-bis(4-idrossi-3-metilstiril)-N-(4-clorofenil)-1H-pirazolo-1-carbossamide (3b). Il composto 3b ha dimostrato attivit anti-HIV con IC50 >3,71 M e CC50 3,71 M, tuttavia l'attivit risultata inferiore a quella del farmaco standard zidovudina.

Une s rie de 11 analogues de la curcumine a t soumise une pr diction des propri t s mol culaires et une valuation de la similarit m dicamenteuse l'aide des logiciels Molinspiration et MolSoft, ainsi qu' une valuation des param tres de lipophilie et de solubilit l'aide du programme ALOGPS 2.1. Les compos s respectant la r gle des cinq de Lipinski ont t synth tis s pour un criblage anti-VIH en tant que m dicaments/pistes biodisponibles par voie orale. La structure des compos s synth tis s a ensuite t confirm e par des analyses spectrales (IR, RMN et masse) et les compos s (3a-k) ont t valu s pour leur activit anti-VIH selon le protocole standard. Le score maximal du mod le de similarit m dicamenteuse (1,1,0) a t obtenu pour le 3,5-bis(4-hydroxy-3-m thylstyryl)-N-(4-chloroph nyl)-1H-pyrazole-1-carboxamide (3b). Le compos 3b s'est av r avoir une activit anti-VIH avec une CI50 > 3,71 M et une CC50 de 3,71 M, mais son activit s'est r v l e inf rieure celle du m dicament standard, la zidovudine.

Eine Reihe von 11 Curcumin-Analoga wurde einer Vorhersage der molekularen Eigenschaften und der Arzneimittel hnlichkeit durch die Software Molinspiration und MolSoft sowie einer Bestimmung der Lipophilie- und L slichkeitsparameter mit dem Programm ALOGPS 2.1 unterzogen. Die Verbindungen, die der "F nf-Regel" von Lipinski folgten, wurden f r das Anti-HIV-Screening als oral bioverf gbare Arzneimittel/Leitstrukturen synthetisiert. Anschlie end wurde die Struktur der synthetisierten Verbindungen durch Spektralanalysen (IR, NMR und Masse) best tigt, und die Verbindungen (3a-k) wurden gem dem Standardprotokoll auf ihre Anti-HIV-Aktivit t untersucht. Der maximale Wirkstoff hnlichkeits-Modellwert (1,1,0) wurde f r 3,5-Bis(4-hydroxy-3-methylstyryl)-N-(4-chlorphenyl)-1H-pyrazol-1-carboxamid (3b) gefunden. Die Verbindung 3b zeigte eine Anti-HIV-Aktivit t mit IC50 >3,71 M und CC50 3,71 M, jedoch war die Aktivit t geringer als die des Standardmedikaments Zidovudin.

This book examines the public stockholding policies of selected developing countries from the perspective of WTO rules and assesses whether the provisions of the Agreement on Agriculture (AoA) could hamper these countries’ efforts to address the challenges of food security. Further, it highlights the need to amend the provisions of the AoA to make WTO rules just and fair for the millions of people suffering from hunger and malnutrition in developing countries. This book highlights that 12 countries namely China, Egypt, India, Indonesia, Jordan, Kenya, Morocco, Pakistan, Tunisia, Turkey, Zambia and Zimbabwe are facing or will face problems in implementing the food security policies due to the provisions under AoA. These provisions need to be amended for permitting developing countries to address hunger and undernourishment. Progress in WTO negotiations on public stockholding for food security purposes are also discussed and analysed. The findings of this study greatly benefit trade negotiators, policymakers, civil society, farmers groups, researchers, students and academics interested in issues related to the WTO, agriculture and food security.

This book examines the public stockholding policies of selected developing countries from the perspective of WTO rules and assesses whether the provisions of the Agreement on Agriculture (AoA) could hamper these countries’ efforts to address the challenges of food security. Further, it highlights the need to amend the provisions of the AoA to make WTO rules just and fair for the millions of people suffering from hunger and malnutrition in developing countries. This book highlights that 12 countries namely China, Egypt, India, Indonesia, Jordan, Kenya, Morocco, Pakistan, Tunisia, Turkey, Zambia and Zimbabwe are facing or will face problems in implementing the food security policies due to the provisions under AoA. These provisions need to be amended for permitting developing countries to address hunger and undernourishment. Progress in WTO negotiations on public stockholding for food security purposes are also discussed and analysed. The findings of this study greatly benefit trade negotiators, policymakers, civil society, farmers groups, researchers, students and academics interested in issues related to the WTO, agriculture and food security.