目的:有时长期难以预测治疗药物和毒性药物的临床疗效和潜在风险。因此,需要进行文献检索以评估临床实践中使用的药物的毒性和较低功效的原因。
方法:因此,搜索有关理化性质的文献,化学式,分子量,pH值,电离,受体类型,激动剂和拮抗剂,治疗性的,化合物与药效团和毒性团的毒性和结构-活性关系,以确定高效和相对低毒性的药物。纳入标准是在PubMed上发表的手稿,Scopus,WebofScience,PubMedCentral,谷歌学者等等,1960年至2023年。关键词如药效团,毒物,结构-活动-关系和疾病也在那里搜索。排除标准是缺乏药效团的化学物质,1960年以前出版的有毒物质和手稿。
结果:研究结果表明,药效基团和毒性基团决定了治疗的临床疗效和安全性,但是如果它们重叠,治疗和毒性作用同时发生。因此,官能团,剂量,共同给药和药物在受体的浓度,药物-受体结合和受体结合的持续时间是药效团和毒性团活性的决定因素。分子质量,化学配置,pH值,受体亲和力和结合能力,多种药效,该化学物质的亲水/亲脂性质极大地有助于药效团和毒性团的功能性。
结论:每日单一治疗,避免可逆药理学,具有共价加合物的药物,维持治疗剂量,并且使用多种药效团来治疗终末期疾病将使毒性最小化并提高疗效。
OBJECTIVE: Sometimes clinical efficacy and potential risk of therapeutic and toxic agents are difficult to predict over a long period of time. Hence there is need for literature search with a view to assessing cause of toxicity and less efficacy of drugs used in clinical practice.
METHODS: Hence literatures were searched for physicochemical properties, chemical formulas, molecular masses, pH values, ionization, receptor type, agonist and antagonist, therapeutic, toxic and structure-activity relationship of chemical compounds with pharmacophore and toxicophore, with a view to identifying high efficacious and relative low toxic agents. Inclusion criteria were manuscripts published on PubMed, Scopus, Web of Science, PubMed Central, Google Scholar among others, between 1960 and 2023. Keywords such as pharmacophore, toxicophore, structure-activity-relationship and disease where also searched. The exclusion criteria were the chemicals that lack pharmacophore, toxicophore and manuscripts published before 1960.
RESULTS: Findings have shown that pharmacophore and toxicophore functional groups determine clinical efficacy and safety of therapeutics, but if they overlap therapeutic and toxicity effects go concurrently. Hence the functional groups, dose, co-administration and concentration of drugs at receptor, drug-receptor binding and duration of receptor binding are the determining factors of pharmacophore and toxicophore activity. Molecular mass, chemical configuration, pH value, receptor affinity and binding capacity, multiple pharmacophores, hydrophilic/lipophilic nature of the chemical contribute greatly to functionality of pharmacophore and toxicophore.
CONCLUSIONS: Daily single therapy, avoidance of reversible pharmacology, drugs with covalent adduct, maintenance of therapeutic dose, and the use of multiple pharmacophores for terminal diseases will minimize toxicity and improve efficacy.