Design of New Thiadiazole Derivatives with Improved Antidiabetic Activity  

作　　者：Chiépi Nadège Dominique Dou Georges Stéphane Dembele Mamadou Guy-Richard Kone Nanou Tiéba Tuo Fandia Konate Adama Niare Panaghiotis Karamanis Nahossé Ziao Chiépi Nadège Dominique Dou;Georges Stéphane Dembele;Mamadou Guy-Richard Kone;Nanou Tiéba Tuo;Fandia Konate;Adama Niare;Panaghiotis Karamanis;Nahossé Ziao(Laboratoire de Thermodynamique et de Physico-Chimie du Milieu, Université NANGUI ABROGOUA, Abidjan, Cô,te-d’Ivoire;Groupe Ivoirien de Recherches en Modélisation des Maladies (GIR2M), Université NANGUI ABROGOUA, Abidjan, Cô,te-d’Ivoire;E2S UPPA, CNRS, IPREM, Université de Pau et des Pays de l’Adour, Pau, France;Laboratoire de Physique Fondamentale et Appliquée, UFR SFA, Université NANGUI ABROGOUA, Abidjan, Cô,te-d’Ivoire)

机构地区：[1]Laboratoire de Thermodynamique et de Physico-Chimie du Milieu, Université NANGUI ABROGOUA, Abidjan, Cô,te-d’Ivoire [2]Groupe Ivoirien de Recherches en Modélisation des Maladies (GIR2M), Université NANGUI ABROGOUA, Abidjan, Cô,te-d’Ivoire [3]E2S UPPA, CNRS, IPREM, Université de Pau et des Pays de l’Adour, Pau, France [4]Laboratoire de Physique Fondamentale et Appliquée, UFR SFA, Université NANGUI ABROGOUA, Abidjan, Cô,te-d’Ivoire

出　　处：《Computational Chemistry》2023年第3期67-80,共14页计算化学（英文）

摘　　要：Diabetes is a serious, long-term (or chronic) disease that occurs when a person’s blood sugar levels are high because their body cannot produce enough insulin, or does not produce enough insulin or that it cannot effectively use the insulin it produces. According to the literature, this disease has several causes, but certain types of diabetes such as type 2 diabetes are most closely linked to a metabolic disorder due to abdominal obesity. Thus, the number of individuals with type 2 diabetes is increasing. It is with this in mind that we work to improve human health. The aim of this study is to design new derivatives of 1,3,4-thiadiazole with improved antidiabetic activity by the mathematical model of multiple linear regression (MLR) established previously. The analysis of the effect on the substituents influencing the antidiabetic activity, fourteen (14) new molecules coded CDTH were generated and presenting values of the potential of inhibitory concentration higher than that of the base compound (pIC50 = 2.526). But thirteen (13) of these new compounds belong to the domain of applicability of the MLR model established previously. In addition, the thermodynamic quantities of formation formed at 298K have been calculated. Lipinski’s rule and pharmacokinetic properties proved that five (5) (TH4, TH9, TH10, TH13 and TH14) new molecules can be used as diabetes medicine.Diabetes is a serious, long-term (or chronic) disease that occurs when a person’s blood sugar levels are high because their body cannot produce enough insulin, or does not produce enough insulin or that it cannot effectively use the insulin it produces. According to the literature, this disease has several causes, but certain types of diabetes such as type 2 diabetes are most closely linked to a metabolic disorder due to abdominal obesity. Thus, the number of individuals with type 2 diabetes is increasing. It is with this in mind that we work to improve human health. The aim of this study is to design new derivatives of 1,3,4-thiadiazole with improved antidiabetic activity by the mathematical model of multiple linear regression (MLR) established previously. The analysis of the effect on the substituents influencing the antidiabetic activity, fourteen (14) new molecules coded CDTH were generated and presenting values of the potential of inhibitory concentration higher than that of the base compound (pIC50 = 2.526). But thirteen (13) of these new compounds belong to the domain of applicability of the MLR model established previously. In addition, the thermodynamic quantities of formation formed at 298K have been calculated. Lipinski’s rule and pharmacokinetic properties proved that five (5) (TH4, TH9, TH10, TH13 and TH14) new molecules can be used as diabetes medicine.

关 键 词：DESIGN Antidiabetic Activity 1 3 4-Thiadiazole Lipinski’s Rule 

分 类 号：R58[医药卫生—内分泌]