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喹诺酮是目前临床上广泛使用的一类广谱、高效、低毒性的一线抗感染化疗药物,主要用于治疗由细菌感染引起的消化道、泌尿道和呼吸道等系统性疾病。但由于不合理用药,细菌对这类药物的耐药性不断增加,因此,寻找能够克服细菌耐药性的更具特点的新型拓扑异构酶抑制剂已成为抗菌领域的研究重点之一。经过药物化学家的孜孜探索,近年来已发现若干类新型拓扑异构酶抑制剂,其中喹诺酮类似物异噻唑喹诺酮和喹唑啉二酮在克服耐药性方面极具潜力,而喹诺酮与其它抗菌剂如利福霉素和口恶唑烷酮形成的杂合体药物在对付喹诺酮耐药菌以及对二者均耐药的细菌感染方面可能大有作为。除已知的香豆素类抑制剂外,以拓扑异构酶中的非喹诺酮键合区为作用靶点的新型抑制剂不断涌现,其中喹啉类抑制剂的体内外活性和治疗效果均令人满意,而具有双重作用机制的苯并咪唑及吡唑类抑制剂对耐药菌虽然具有优秀的体外活性,但其体内活性并不理想。此外,筛选技术的不断改进以及高通量筛选技术的广泛应用也为进一步寻找新到的拓扑异构酶抑制剂带来更多的希望。
Quinolones are currently a widely used first-line anti-infective chemotherapeutic drugs widely used clinically in the treatment of systemic diseases such as the digestive tract, urinary tract and respiratory tract caused by bacterial infections. However, due to unreasonable drug use, bacterial resistance to these drugs has been increasing. Therefore, finding more novel topoisomerase inhibitors that can overcome bacterial resistance has become a research focus in the field of antibacterials. In recent years, several novel topoisomerase inhibitors have been explored by medicinal chemists. Quinolone analogues of isothiazol quinolones and quinazolinediones have great potential in overcoming drug resistance. Quinolone and other antibacterials Agents such as rifamycins and oxazolidinones may work well in combating quinolone-resistant bacteria and bacterial infections that are resistant to both. In addition to the known coumarin inhibitors, new inhibitors targeting non-quinolone binding domains in topoisomerases are emerging, with quinoline inhibitors both in vitro and in vivo in activity and therapeutic efficacy People are satisfied, and the dual mechanism of action of benzimidazole and pyrazole inhibitors for drug-resistant bacteria despite excellent in vitro activity, but its in vivo activity is not ideal. In addition, the continuous improvement of screening technology and the extensive application of high-throughput screening technology bring more hope for further searching for new topoisomerase inhibitors.