Studies On Bioactivity And Quantitative Structure Activity Relationship (QSAR) Of Analogues Of Pentamidine

Pentamidine is an aromatic diamidino compound .The efficacy of aromatic diamidines in the treatment of protozoal diseases was first recognized in the 1930s by investigators searching for agents with therapeutic activity against African trypanosomiasis . Clinical trials examining the activities of pentamidine revealed that it and its analogues were effective against African trypanosomiasis in the early stages and against leishmaniasis. Pentamidine was discovered as early as 1957 to be an effective agent for the treatment of pneumocystis carinii pneumonia. Aromatic diamidines not only have antiprotazoal activity but also exhibit activity against bacteria, fungi, viruses and tumors. In order to find the compounds , which are more potenter and less expensive than pro-compound, i.e. pentamidine , and according to the known structure-activity relationship in the medical research, we have synthesized thirty-five compounds, which have been identified through MS and ~1HNMR,and studied scientifically the hyphal of phytopathogen. Some interesting results have been found as follows :1) Pentamidne and its analogues have been synthesized ,and also have been identified through MS and ~1HNMR.2) Studies of indoor leaf in vitro experiment and young fruit experiment showed pentamidine and its analogues had potenly against phytopathogen , and the effciency varied with structures. Pentamidine and its analogues showed the inhibition activity ofBotrytis cinerea Pers., Fulvia fulva Cooke, Alternaria brassicae Sacc.m vitro at lOmg/L.especially compounds 2,3{ a , Q-di(4-amidinophenoxy)alkanes}, 12 and 13 { a , ca -di(4-(N-i-Pr)amidino-phenoxy)alkanes} are more potenter than pentamidine against the hyphal of Botrytis cinerea Pers.. compounds 1, 3, 6, 7, 8{a ,gj -di(4-imidazolinophenoxy)alkanes}, 12, 13, 14 and 17 are the most potenter against Fulvia fulva Cooke. Compounds 2, 3, 7, 8, 12, 17, 18{2,2'-dimethoxy-a ,u -di(4-amidinophenoxy)alkanes} and 32 inhibited the mycelial of Alternaria solani Jones et Grout., compounds 1, 2, 3, 5, 12, 13, 14, 17 and 18 against Alternaria brassicae Sacc. and compounds 2, 5 , 12 and 17 inhibited the hyphal of Botryosphaeria dothidea.Ces.etdeNot are more potenter than pentamidine.Only compound 13 was the most potentest than pentmidine against Phytophthora capsici Leonian. Compounds 1 , 2, 3, 5, 7, 11 to 20 and 31 to 33 { a , u -di(3-amidinophenoxy)alkanes} were more potenter than pentamidine against the hyphal of Alter aria alternatn KeisslerDThe protective and therapy effectiveness of indoor leaf in vitro experiment showed that compounds 3 and 12 are more potenter than pentamidine .Young fruit experiment also showed that compounds 1, 2, 3, 7, 11 to 15, 19, 22{2,2'-dimethoxy- a , cj -di(4-imidazolinophenoxy)alkanes}and 34 were more potenter than pentamidine by spraying liquor lh and 24 hrs after inoculation .3) Two quantitative structure-activity equations have been worked out onpentamidine and its analogues by using Hyperchem, Mopac and CODESSAprogramming. The results showed Min e-n attraction for a C-C bond and Max atomic orbitalelectronic population have affected obviously on activities of analogues of Pentamidine...