Venoms classification and therapeutic uses: a narrative review.

The mere glimpse of venomous animals has always terrified humans because of the devastating effects of their venoms. However, researchers across the globe have isolated therapeutically active ingredients from these venoms and continue to explore them for drug leads. These efforts lead to the discovery of therapeutic molecules that the US-FDA has approved to treat different diseases, such as hypertension (Captopril), chronic pain (Ziconotide), and diabetes (Exenatide). The main active constituents of most venoms are proteins and peptides, which gained more attention because of advancements in biotechnology and drug delivery. The utilization of newer screening approaches improved our understanding of the pharmacological complexity of venom constituents and facilitated the development of novel therapeutics. Currently, with many venom-derived peptides undergoing different phases of clinical trials, more are in pre-clinical drug development phases. This review highlights the various sources of venoms, their pharmacological actions, and the current developments in venom-based therapeutics.

An overview on antiepileptic drugs.

Epilepsy is the most common chronic neurological disorder of the brain. For several decades different kinds of medications have been used to treat epilepsy. Even though many surgical advances has been made and implemented, medications remain the basis of treatment. The search for noble antiepileptic drugs (AEDs) with more selective activity and lower toxicity continues to be an area of intensive investigation in medicinal chemistry. Additionally, drug resistance is an important clinical problem in epilepsy and is associated with an increased risk of morbidity and mortality. This review intends to present a comprehensive overview on AED in particular along with discussion on some aspects of associated drug resistance and combination therapy.

Modified PLA nano in situ gel: a potential ophthalmic drug delivery system.

A novel nano in situ gel forming system of 5-Fluorouracil (5-FU) was investigated for its potential use for conjunctival/corneal squamous cell carcinoma (CCSC). The study was conducted in two steps, in the first step PLA nanoparticles were prepared and characterized; in the second step the drug loaded PLA nanoparticles were dispersed in sodium alginate solution yielding the modified nano in situ system, which were evaluated in rabbit eye. Size and morphology of prepared PLA particles were verified by using dynamic light scattering (DLS), atomic force microscope (AFM) and scanning electron microscope (SEM). In vitro and in vivo study of free 5-FU, PLA nanoparticles and modified nano in situ system were conducted in simulated tear fluid and in rabbit eye respectively. PLA nanoparticles were in size range of 128-194 nm with spherical shape and smooth surface with narrow size distribution. No polymer drug interaction was found as confirmed by FTIR, NMR and DSC. XRD of PLA nanoparticles confirmed that 5-FU was present in the crystalline state. In vitro experiments indicated a diffusion controlled release of 5-FU from both PLA nanoparticles and modified nano in situ system with high burst effect. Modified nano in situ gel system (MNS) significantly increased the Cmax and AUC0-8 in aqueous humor as compared to 5-FU solution and PLA nanoparticles. Higher 5-FU level in aqueous humor was possibly because of increased retention time of gel matrix-embedded drug loaded nanoparticles. Overall results showed the potential of MNS for ophthalmic delivery in the therapy of CCSC.

Benzoxazinones as Human Peroxisome Proliferator Activated Receptor Gamma (PPARγ) Agonists: A Docking Study Using Glide.

The purpose of the present study is to undertake a docking study of some benzoxazinone derivatives on human peroxisome proliferator activated receptor co-crystallized with an alpha-aryloxyphenylacetic acid agonist using Glide 4.5. The QikProp program was used to obtain the absorption, distribution, metabolism and excretion properties of the analogues. The intermolecular hydrogen bonding interaction of the best-fit ligands were found to be associated with Tyr473, Ser289, Hie 449, Hip 323, Ser 342 and Gly 284 amino acid residue at the receptor active site. Among all the observed interaction with similar binding pattern, the presence of methyl carboxypentyl side chain (Lig. No. 21) showed additional interaction with Ser 342 and the affinity was increased by carboxyl oxygen (as hydrogen bond acceptor) with a best Glide score of -14.54 as compared to the co-crystallized aryloxyphenyl acetic acid which achieved a glide score of -12.50.

Design, synthesis, anticonvulsant screening and 5HT1A/2A receptor affinity of N(3)-substituted 2,4-imidazolidinediones and oxazolidinediones.

In the present study, a series of N(3)-substituted 2,4-imidazolidinediones and oxazolidinediones derivatives (1-16) were synthesized and tested for anticonvulsant activity using the maximal electroshock seizure test. Affinity towards receptor (5-HT1A/2A) was also studied. Their neurotoxicity was determined using the rotarod test. Structures of compounds were confirmed by spectroscopic methods. Compounds 1, 2, 5, 7, 9, and 10 exhibited significant anticonvulsant activity as compared to the standard drug phenytoin. Affinity toward receptor (5-HT1A/2A) was studied in vivo for compounds 1, 2, 5, 7, 9, and 10. Rectal body temperature, lower lip retractions and head twitch responses in Wistar rats/albino mice were determined for this purpose. The tested compounds showed affinity for 5-HT1A and 5-HT2A receptors (agonists/antagonists and presynaptic/postsynaptic). Replacement of piperazine by aniline derivatives provides good outcomes in terms of affinity for 5-HT1A/2A.

Codrug: an efficient approach for drug optimization.

Codrug or mutual prodrug is an approach where various effective drugs, which are associated with some drawbacks, can be modified by attaching with other drugs of same or different categories directly or via a linkage. More appropriately one can say combining two different pharmacophores with similar or different pharmacological activities elicit synergistic action or help to target the parent drug to specific site/organ/cells respectively. This approach is commonly used to improve physicochemical, biopharmaceutical and drug delivery properties of therapeutic agents.

Development in malarial vaccine: A review.

Malaria, a vector-borne infectious disease, is currently a grave and universal concern with a significant social, economic, and human cost, mainly in developing countries. In addition, the emergence and spread of resistance to antimalarial therapies have further aggravated the global situation. Currently most of the research is focused on development of antimalarial drugs, drug resistance, and novel formulations to maximize the therapeutic effect. A number of novel molecules potentially active against malarial parasites are being developed. A vaccine is still viewed as a critical part of a long-term malaria control strategy. In the last several years various studies have shown significant progress in the development of vaccines against malaria. Advancement in vaccine technology and immunology is being used to develop malaria subunit vaccines that would open up new vistas for effective treatment and control of malaria. The development of an effective malaria vaccine represents one of the most important approaches that would provide a cost-effective intervention in addition to currently available malaria control strategies. An overview on progress in antimalarial vaccines is presented.