System xc− (Sxc−), a cystine‐glutamate antiporter, is established as an interesting target for the treatment of several pathologies including epileptic seizures, glioma, neurodegenerative diseases, and multiple sclerosis. Erastin, sorafenib, and sulfasalazine (SSZ) are a few of the established inhibitors of Sxc−. However, its pharmacological inhibition with novel and potent agents is still very much required due to potential issues, for example, potency, bioavailability, and blood–brain barrier (BBB) permeability, with the current lead molecules such as SSZ. Therefore, in this study, we report the synthesis and structure–activity relationships (SAR) of SSZ derivatives along with molecular docking and dynamics simulations using the developed homology model of xCT chain of Sxc− antiporter. The generated homology model attempted to address the limitations of previously reported comparative protein models, thereby increasing the confidence in the computational modeling studies. The main objective of the present study was to derive a suitable lead structure from SSZ eliminating its potential issues for the treatment of glioblastoma multiforme (GBM), a deadly and malignant grade IV astrocytoma. The designed compounds with favorable Sxc− inhibitory activity following in vitro Sxc− inhibition studies, showed moderately potent cytotoxicity in patient‐derived human glioblastoma cells, thereby generating potential interest in these compounds. The xCT‐ligand model can be further optimized in search of potent lead molecules for novel drug discovery and development studies.

System [Formula: see text] is an antiporter belonging to the hetero(di)meric amino acid transporter family. It is located on astrocytes as well as on blood-brain barrier within the CNS. It plays a pivotal role in free radical neutralization as well as neuronal signalling by regulating the glutathione production which occurs via the exchange of intracellular glutamate with extracellular cystine at 1:1 molar ratio. Understandably, it is a vital component responsible for the maintenance of neuronal homeostasis (e.g. redox state). Hence, it could be postulated that any perturbation in system [Formula: see text] function may contribute, directly or indirectly, to the pathophysiology of a variety of CNS disorders like Alzheimer's disease, schizophrenia, drug addiction, depression, multiple sclerosis, hypoglycemic neuronal cell death, glioma, and excitotoxicity, making system [Formula: see text] a promising target for treating CNS disorders. In recent times, recognizing the potential of this target, variety of inhibitors has been synthesized by modifying commercially available potent inhibitors including sulfasalazine, erastin, and sorafenib. Although, they have demonstrated efficacy, the in-depth data is still lacking to warrant their use for the treatment of aforementioned CNS disorders. In this review, we discuss the in-depth role of system [Formula: see text] transporter in maintaining normal physiology as well as in the pathophysiology of CNS diseases. Additionally, we have also listed some of the potent inhibitors of system [Formula: see text]. In conclusion, the critical role of system [Formula: see text] in multiple CNS disorders and advanced research on its inhibitors have promising future prospects for better management of the CNS ailments.

Pulsatile  Drug  Delivery  Systems  are  gaining  a  lot  of  interest  as  they  deliver  the  drug  at  the  right  place  at  the  right  time  and  in  the  right  amount,  thus  providing  spatial  and  temporal  delivery  and  increasing  patient  compliance.  These  systems  are  designed  according  to  the  circadian  rhythm  of  the  body.  The  principle  rationale  for  the  use  of  pulsatile  release  of  the  drugs is where  a  constant  drug  release  is  not  desired.  A  pulse  has  to  be  designed  in  such  a  way  that  a  complete  and  rapid  drug  release  is  achieved  after  the  lag  time.  Various  systems  like  capsular  systems,  osmotic  systems,  single-  and  multiple-unit  systems  based  on  the  use  of  soluble  or  erodible  polymer  coating  and  use  of  rupturable  membranes  have  been  dealt  with  in  the  article.  It  summarizes  the  latest  technological  developments,  formulation  parameters,  and  release  profiles  of  these  systems.  These  systems  are  beneficial  for  the  drugs  having  chronopharmacological  behavior  where  night  time  dosing  is  required,  such  as  anti-arhythmic  and  anti-asthmatic.

Aim:This study was carried out to evaluate the effect of Vigna mungo hydroalcoholic extract (VMHA) by papain induced osteoarthritis (OA) in the rat model.Materials and Methods:OA was induced by intra-articular injection of papain (4% w/v) along with cysteine (0.03 M) on day 1, 4 and 7 in rats and VMHA was administered orally in three doses (100, 200 and 400 mg/kg) after last papain injection. The anti-osteoarthritic activity was evaluated by measuring knee joint diameter, grip strength, locomotion activity and hanging time. Histopathological analysis and acute toxicity study were also performed.Results:VMHA improved inflammatory condition with all the doses, but significant (P < 0.05) attenuation of inflammation was present only with 400 mg/kg dose. The grip strength, locomotion activity and hanging time were also significantly (P < 0.05) improved at dose level of 100 mg/kg however other two doses (200 mg/kg and 400 mg/kg) were not found to be effective. VMHA did not show any mortality or any toxic clinical signs after oral administration of 2 g/kg dose.Conclusion:VMHA improved arthritic condition by significantly reducing pain and inflammation.

Cerebral amyloid angiopathy (CAA) is a cause of intracerebral hemorrhage in a significant proportion of normotensive patients. Two cases of pathologically proved multiple intracerebral hemorrhages due to CAA are reported. These hemorrhages are accurately demonstrated on computed tomography and are typically superficial in location. CAA should be considered as a cause of such hemorrhages in elderly patients who are often normotensive and demented.