The effect on the bioactivity of antibacterial sulfonamide drugs against malaria and tuberculosis via an increase of the lipid solubility groups by condensation with a reduced chalcone was investigated. Sulfonamide derivatives (8a–8d) were obtained via a 1,3-diarylpropane scaffold, prepared by reduction of the relevant chalcones, followed by the addition of a sulfonamide moiety via the Mannich and the Mannich exchange reactions. The ClogP values indicated that the lipophilicities of 8a–8d and intermediate reduced chalcones and N-alkylated reduced chalcones (5a–7a) were much higher than those of the sulfonamides (1a–1c). The N-alkylated reduced chalcone derivatives 6 and 7 exhibited the highest antimalarial (Plasmodium falciparum (NF54 strain)) activity. Addition of the sulfonamide group weakened the activity, even though some ClogP values were higher, while 1a–1c showed no activity. The reduced chalcones 5a and 5 showed potent growth inhibition of Mycobacterium tuberculosis (H37Rv strain), but the sulfonamide derivatives 8a and 8d showed no or insignificant activity (0 and 14%, respectively) against M. tuberculosis, despite high ClogP values. Thus, the possible increase in bioactivity expected from an increase in ClogP values (lipophilicity) might be counteracted by the higher molecular weight of the studied analogues.

中文翻译：

---

含磺酰胺侧链的还原查耳酮的合成及生物活性

研究了通过与减少的查尔酮缩合增加脂类溶解性基团，对抗菌素磺胺类药物对疟疾和结核病的生物活性的影响。磺酰胺衍生物（8a – 8d）是通过1,3-二芳基丙烷骨架获得的，该骨架是通过还原相关的查耳酮而制备的，然后通过曼尼希（Mannich）和曼尼希（Mannich）交换反应添加磺酰胺部分。ClogP值表明，8a – 8d以及中间还原的查耳酮和N-烷基化还原的查耳酮（5a – 7a）的亲脂性远高于磺酰胺类药物（1a – 1c））。N-烷基化的还原查耳酮衍生物6和7表现出最高的抗疟疾（恶性疟原虫（NF54株））活性。即使有些ClogP值较高，磺酰胺基团的加入也会减弱活性，而1a – 1c则没有活性。还原的查耳酮5a和5对结核分枝杆菌（H37Rv株）表现出有效的生长抑制作用，但磺酰胺衍生物8a和8d对结核分枝杆菌无活性或微不足道的活性（分别为0和14％）。，尽管ClogP值较高。因此，预期的ClogP值增加（亲脂性）可能会提高生物活性，这可能是由于所研究类似物的较高分子量所抵消。