Recent Breakthroughs in Various Antimicrobial Resistance Induced Quorum Sensing Biosynthetic Pathway Mediated Targets and Design of their Inhibitors.

Objective: The world is under the grasp of dangerous post-antibiotics and antimicrobials attack where common infections may become untreatable, leading to premature deaths due to antimicrobial resistance (AMR). While an estimated 7,00,000 people die annually due to AMR, which is a public health threat to all communities in different parts of the world regardless of their economic status; however, this threat is serious in low- and middle-income countries having lack of sanitation and health infrastructure. The 68th World Health Assembly endorsed the Global Action Plan on antimicrobial resistance.

Chitosan Anchored Nanoparticles in Current Drug Development Utilizing Computer-Aided Pharmacokinetic Modeling: Case Studies for Target Specific Cancer Treatment and Future Prospective.

Background: Recently, in the medical and pharmaceutical fields, biopolymers are extensively used for chemical and mechanical modifications of pharmaceutical dosage forms, which add novel properties, functions, and applications. Structural modification of dosage form by polymers along with redesigning in pharmaceutical and tissue engineering fields, presently being the center of analysis for the modern research world, which utilizes the subtle instruments, precise research strategies and most significantly the excipients.

Method: The polymer, chitosan, which is a natural linear polysaccharide composed of randomly distributed β-(1- 4)-linked D-Glucosamine and N-acetyl-D-Glucosamine units.

Current Development on Chitosan-based Antimicrobial Drug Formulations for the Wound Healing.

Background: Derived from polyose, chitosan is an outstanding natural linear polysaccharide comprised of random arrangement of β-(1-4)-linked D-Glucosamine and N-acetyl-DGlucosamine units.

Objective: Researchers have been using chitosan as a network forming or gelling agent with economically available, present polyose, low immunogenicity, biocompatibility, non-toxicity, biodegradability, protects against secretion from irritation and don't suffer the danger of transmission animal infective agent.

Methods: Furthermore, recent studies gear up the chitosan used in the development of various biopharmaceutical formulations, including nanoparticles, hydrogels, implants, films, fibers, etc.

QSAR and molecular docking studies of lethal factor protease inhibitors against .

is considered as a biological warfare agent because it is the causative agent of the serious infectious anthrax disease. Delay in treatment leads to lethal factor-mediated toxaemia which is very critical due to lack of therapeutic options. Consequently, attempts have been made to discover potent lethal factor (LF) protease inhibitors such as small-molecule synthetic 2-thio-1,3-thiazolidine-4-one (rhodanine) compounds.

In-Silico Modeling in Drug Metabolism and Interaction: Current Strategies of Lead Discovery.

Background: Drug metabolism is a complex mechanism of human body systems to detoxify foreign particles, chemicals, and drugs through bio alterations. It involves many biochemical reactions carried out by invivo enzyme systems present in the liver, kidney, intestine, lungs, and plasma. After drug administration, it crosses several biological membranes to reach into the target site for binding and produces the therapeutic response.

Perspective and Potential of A2A and A3 Adenosine Receptors as Therapeutic Targets for the Treatment of Rheumatoid Arthritis.

Adenosine is a purine nucleoside which is an effective controller of inflammation. The inflammatory effect of adenosine is expressed via its four receptor subtypes viz. A1, A2A, A2B and A3.

Identification of Therapeutically Active Molecules against Anthrax through Structure and Ligand based Drug Design.

Background: People suffer from fatal diseases which are responsible for mortality. Potent devices and medicines are being developed to fight diseases caused by the microorganism for saving the lives of individuals. Highly pathogenic viruses and bacteria are being incorporated into biological warfare, which has become a major threat to mankind and causes the destruction of lives in a short span of time.

Current Breakthroughs in Structure-based Design of Synthetic and Natural Sourced Inhibitors Against Zika Viral Targets.

Background: Zika is a worldwide pandemic dreadful viral transmission through Aedes mosquito vector. It significantly causes fever, joint pain or rash, and conjunctivitis. Pregnant mothers suffering from Zika viral infection may have fetal abnormalities due to severe neurological problems, characterized by microcephaly along with Guillain-Barré syndrome, issuing ZIKV a major public health concern as declared by the World Health Organization.

Combinatorial design and virtual screening of potent anti-tubercular fluoroquinolone and isothiazoloquinolone compounds utilizing QSAR and pharmacophore modelling.

The virulence of tuberculosis infections resistant to conventional combination drug regimens cries for the design of potent fluoroquinolone compounds to be used as second line antimycobacterial chemotherapeutics. One of the most effective in silico methods is combinatorial design and high throughput screening by a ligand-based pharmacophore prior to experiment. The combinatorial design of a series of 3850 fluoroquinolone and isothiazoloquinolone compounds was then screened virtually by applying a topological descriptor based quantitative structure activity relationship (QSAR) for predicting highly active congeneric quinolone leads against Mycobacterium fortuitum and Mycobacterium smegmatis.

Aegeline inspired synthesis of novel amino alcohol and thiazolidinedione hybrids with antiadipogenic activity in 3T3-L1 cells.

Excess adiposity is a hallmark of obesity, which is caused due to an imbalance between energy intake and energy consumed. Obesity is often associated with several metabolic disorders like dyslipidemia, cardiovascular diseases and type 2 diabetes. Earlier, our group had reported natural product Aegeline (amino-alcohol) isolated from the plant Aegle marmelos as an anti-diabetic and anti-dyslipidemic compound.

Curcumin-3,4-Dichloro Phenyl Pyrazole (CDPP) overcomes curcumin's low bioavailability, inhibits adipogenesis and ameliorates dyslipidemia by activating reverse cholesterol transport.

Background: Adipocyte dysfunction, obesity and associated metabolic disorders are of prime healthcare concern worldwide. Among available medications, natural products and inspired molecules hold 40% space in clinically prescribed medicines. In queue, this study overcomes the drawback of curcumin's low bioavailability with potent anti-adipogenic and anti-dyslipidemic activity.

Recent Advances in Ligand and Structure Based Screening of Potent Quorum Sensing Inhibitors Against Antibiotic Resistance Induced Bacterial Virulence.

Background: Antibiotic resistance is a growing threat in the treatment of bacterial diseases. Bacterial invasion and its virulence can cause damage to the host cells via quorum sensing mechanism which is responsible for the intercellular communication among bacteria that regulates expression of many genes. Quorum sensing (QS) differentially expresses specific sets of genes which may produce resistance.

In-silico combinatorial design and pharmacophore modeling of potent antimalarial 4-anilinoquinolines utilizing QSAR and computed descriptors.

There are very few studies for combinatorial library design and high throughput screening of 4-anilinoquinoline antimalarial compounds having activities against parasitic strain of . Therefore, an attempt has been made in the present paper to design potent lead compounds in this congener utilizing quantitative structure activity relationship utilizing theoretical molecular descriptors. QSAR models for a series of 4-anilinoquinolines considering various theoretical molecular descriptors including topological, constitutional, geometrical, functional group and atom-centered fragments has been carried out by stepwise forward-backward variable selections assimilating multiple linear regression (MLR) methods showing the topological indices contribute maximum impact on parasitic strain.

Modelling inhibition of avian aromatase by azole pesticides.

The potential effects of pesticides and their metabolites on the endocrine system are of major concern to wildlife and human health. In this context, the azole pesticides have earned special attention due to their cytochrome P450 aromatase inhibition potential. Cytochrome P450 aromatase (CYP19) catalyses the conversion of androstenedione and testosterone into oestrone and oestradiol, respectively.

Molecular modelling studies on 2-substituted octahydropyrazinopyridoindoles for histamine H2 receptor antagonism.

The human histamine H2 receptor (hH2HR) is a G-protein coupled receptor protein with seven transmembrane (TM)-spanning helices primarily involved in regulation of gastric acid secretion. Antagonists targeting hH2HR are useful in the treatment of hyperacidic conditions such as peptic ulcers, gastresophageal reflux disease and gastrointestinal bleeding. We have previously reported the antagonism of 2-substituted pyrazinopyridoindoles at the human histamine H1 receptor and mode of binding of these compounds at the hH1HR using in silico methods.

QSAR of Chalcones Utilizing Theoretical Molecular Descriptors.

The paper is an attempt for QSAR modeling based on topological, electrostatic, quantum chemical, constitutional, geometrical and physicochemical indices computed from the structures of 59 set of synthesized chalcone derivatives tested for the cell cycle inhibition of mitotic G2/M phase using multiple linear regression method. Impact of such computed structural descriptors towards antimitotic and antiproliferative activities was analysed by ridge regression (RR) studies. The RR model explained that the topological indices alone can produce significant influence upon the pharmacological responses while combination of topological, electrostatic and quantum chemical descriptors can enhance the degree of impact towards antimitotic and antiproliferative activities of these compounds.

Homology modeling and virtual screening of inhibitors against TEM- and SHV-type-resistant mutants: A multilayer filtering approach.

TEM and SHV are class-A-type β-lactamases commonly found in Escherichia coli and Klebsiella pneumoniae. Previous studies reported S130G and K234R mutations in SHVs to be 41- and 10-fold more resistant toward clavulanic acid than SHV-1, respectively, whereas TEM S130G and R244S also showed the same level of resistance. These selected mutants confer higher level of resistance against clavulanic acid.