ABSTRACT
After years of viewing cirrhosis as the irreversible end-stage of liver fibrosis, it has been shown recently that the possibility of its reversal is no longer a dream. Several studies on experimental animal models showed possible spontaneous resolution of fibrosis after the removal of fibrogenic stimulus. Similar results were also observed in human patients with liver fibrosis due to autoimmune hepatitis and biliary etiology. However, the need for other means of treatment is urgent, especially when the removal of the causative factor is unlikely. Recent antifibrotic strategies were designed to target one or more of the three stages involved in the process of fibrosis. These are the triggering stage, fibrogenesis, and extracellular matrix accumulation. In this review, the classification of the current drugs or agents that showed inhibition of one or more of fibrosis stages with their chemical synthesis are presented.
Subject(s)
Drug Discovery/trends , Liver Cirrhosis/drug therapy , Liver/drug effects , Animals , Humans , Liver/pathology , Liver Cirrhosis/pathologyABSTRACT
A formal total synthesis of (-)-cephalotaxine (1) has been achieved. The key step is an intramolecular aldol condensation of the diketone 9, which in turn was obtained in three steps from the azabicyclic compound 6 derived from D-proline according to Seebach's procedure. Treatment of 9 with a catalytic amount of sodium 2-methyl-2-butanolate in benzene at room temperature gave the alpha, beta-unsaturated ketone 8 in 43% yield. Catalytic hydrogenation of 8 followed by reduction of the ketone 22 with sodium borohydride and acetylation of the resulting alcohol 23 gave the acetoxy derivative 24, which, after deprotection, was acylated with (methylthio)acetic acid to give the amide 26. Compound 26 was converted into optically active ketolactam 4 following the synthetic operations developed for the synthesis of the racemic compound.
Subject(s)
Antineoplastic Agents, Phytogenic/chemical synthesis , Harringtonines/chemical synthesis , Acetylation , Borohydrides , Catalysis , Homoharringtonine , Indicators and ReagentsABSTRACT
A total of 293 cases of various types of leukaemia admitted in Central Hospital (Riyadh) were studied from January 1981 to December 1988. The incidence of leukaemia was worked out to be 0.13% of the total hospital population during this period. Acute non-lymphocytic leukaemia (ANLL) or acute myeloid leukaemia (AML) group was the most frequent (37.54%), followed by acute lymphocytic leukaemia (24.23%) followed by chronic myeloid leukaemia [corrected] (19.11%), chronic lymphocytic leukaemia (CLL) group (18.77%) and lymphosarcoma cell leukaemia (LSCL) (0.35%). Acute leukaemias were further classified into subtypes on the basis of FAB (French-American-British) classification. In ANLL or AML group, the pattern was M2 greater than M4 greater than M3 greater than M6 greater than M1 greater than M5. In ALL group, the pattern was L2 greater than L1 greater than L3. Among FAB subtypes of acute leukaemias, the pattern was L2 greater than M2 greater than M4 greater than M3 greater than M6 greater than M1 and L1 greater than L3 greater than M5. The age range of these patients was 5 years to 80 years; only 9 cases were less than 11 years of age. In childhood and young adults, acute leukaemias (ALL and AML) were the commonest types (particularly ALL was common in childhood), whereas CML was common in adults and CLL in old age. Males dominated the females in all the types of leukaemia (male to female ratio was 2.4:1). Out of 293 leukaemia cases, 149 (51.0%) were Saudi Arabs, the rest were expatriates. AML was found to be the most common type in central, western and southern Saudi Arabia.(ABSTRACT TRUNCATED AT 250 WORDS)
