Background: mTORC1/ PI3K control multiple anabolic pathways, including protein synthesis, ribosome production, lipogenesis, and nucleotide synthesis, are all important for cell and tissue growth. Sapanisertib and Dactolisib inhibit PI3K/AKT/mTOR pathway, an important signaling pathway for many cellular functions such as growth control, metabolism and translation initiation. Methods: Dactolisib contains quinolin-3-yl-2,3-dihydroimidazo[4,5-c]quinolin scaffold and Sapanisertib contains benzo[d]oxazol-5-yl-1-ethyl-1H-pyrazolo[3,4-d]pyrimidinnucleous. From the reference to both of drug novel series of 4-Amino-3-(isoquinolin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin was developed by molecular docking. In sillico analysis was done with SWISSADME online tools. Results: Among all the designed derivatives, compounds 6(-10.6 kcal/mol) , 12( -10.7 kcal/mol), 14( -10.2 kcal/mol), and 16(-10.2 kcal/mol) have a good binding affinity than others. Biological activity was predicted by Molinspirationonline software tool showing that all compounds are active on G- protein coupled receptor. In silico toxicity profile of designed compounds was performed using the SWISSADME program, indicating that all the compounds follow the Lipinski rule of five and do not penetrate Blood brain barrier. Conclusion: Series of pyrazolo[3,4-d]pyrimidin derivatives gives good binding affinity with pan- PI3-Kinese/Mtor inhibitors. The present study provided a better understanding of the molecular modeling requisite for maintaining and/or improving PI3K/mTOR inhibitors.

Background: Histamine, a biological amine, is considered as a principal mediator of many pathological processes regulating several essential events in allergies and autoimmune diseases. Numerous derivatives have been developed that strive with histamine at H1 receptor and prevent binding of histamine at H1 receptor thus prevent allergic reactions. Molecules containing triazole ring fused with six-membered ring systems are found to possess broad applications in the field of medicine and industry. The present study is an attempt to characterize the impact of the nature of the substituent introduced at the 5 positions of the-4H-1,2,4-triazole-3-thiol on their capacities to bind with H1 receptor. Methods: Molecular docking (PDB ID: 3RZE) revealed that synthesized derivatives and target proteins were actively involved in binding with Tyr-108, Thr-112, Ala-216, and Phe432 subunits. The pharmacophore model new 5-(4-substituted phenyl)-4-(phenylamino)- 4-H-1,2,4-triazole-3-thiols (5a-5h) were designed and evaluated for H1-blocking activity using isolated segments from the guinea pig ileum. Results: According to in silico analysis, all the compounds have a topological polar surface area (TPSA) less than 140 Å squared, so they tend to a good penetration in cell membranes. The results show that most of the compounds are non-inhibitors of CYP450 substrates that play a fundamental role in drug metabolism. Compounds 5d (50.53±12.03), 5h (50.62±12.33) and 7a (55.07±12.41) are more active than others. Conclusion: Finally, these derivatives were screened for H1 receptor antagonist activity using guinea pig ileum taking chlorpheniramine maleate as a standard. Most of the compounds possesses better antihistamine activity.

Malaria, a life-threatening disease, is caused by parasitic single-celled microorganisms. It is specifically transmitted by the anopheles female mosquito of the Plasmodium family. There are a lot of drugs available in the market to treat this life-challenging disease. Chloroquine, a cheaper molecule that is available worldwide, is one of them. Drug resistance has been observed with chloroquine as well as with some other quinine derivatives and with artemisinin derivatives in the southeast region of Asia in countries like Cambodia, Thailand, Myanmar, and Vietnam country since 1957. After 1970, the drug resistance has been further increased and it has been expanded in several localities of India. Also, antimalarial agents, particularly chloroquine, have so many side effects such as nausea, vomiting, blurred vision, abdominal cramps, diarrhea, headache, appetite loss, deprivation of hearing, skin color change, baldness, reduced body weight, and seizures. Furthermore, this drug cannot be given to pregnant women. Hence, it is the right time to design and develop newer antimalarial agents so that this kind of drug resistance, as well as side effects of the drugs, can be overcome.

Cancer refers to the group of diseases characterized by uncontrolled growth of abnormal cells. It spreads throughout the body which makes this disease one of the huge global threats to mankind. Intensive research over the years has established deregulation of mam-malian target of rapamycin pathway in cancer. This has led to the development of mammalian target of rapamycin inhibitors. Several inhibitors of the mammalian target of rapamycin are under preclinical and early clinical trials. Researchers have investigated a series of furoquinoline, phenyl sulphonylureas, 4-acrylamido-quinoline, pyrazolochalcones, imidazole [4,5-b] pyridine, thienopyrimidine, aminopyrimidin scaffolds in the last three years. This review provides comprehensive information and critical discussions on designing of novel selective inhibitors of mammalian target of rapamycin with superior activity in the treatment of cancer. 

NADP-dependent enzyme Glutamate dehydrogenase is responsible for the maintenance of reduced state in plasmodia. Chloroquine and Mefloquine inhibit glutamate dehydrogenase enzyme and also glutathione reductase like antioxidative enzyme and thioredoxin, inducing oxidative stress. Plasmodia can't survive in the highly oxidized medium. From a detailed study on the SAR of quinolines, a series of compounds were designed and developed using molecular docking, In silico analysis was done using SWISSADME online tool, and bioactivity prediction was performed using Molinspiration online tool. Among the all designed compounds, in the benzotriazole series, compound code 1(d) (-103.22kcal/mol), 1(e) (-102.05kcal/mol), and 1(b) (-100.78 kcal/mol) show good binding affinity. Whereas, in the benzimidazole series, compound code 2(f) (-104.98 kcal/mol), 2(b) (-104.86kcal/mol) and 2(g) (-104.08kcal/mol) shows good binding affinity. The performed research reveals that benzimidazole derivatives offer an advantage over benzotriazole moiety for binding affinity with the enzyme Plasmodium Falciparum glutamate dehydrogenase.