Exploration of Novel 5α-Reductase Inhibitors for Benign Prostatic Hyperplasia by 2D/3D QSAR, Cytotoxicity Pre-ADME and Docking Studies.

Background: 5α-Reductase (5AR), an NADPH dependent enzyme, is expressed in most of the prostate epithelial cells. By converting testosterone (T) into more potent androgen dihydrotestosterone (DHT), it plays an important role in men physiology and represents an efficient therapeutic target for androgen-dependent diseases. Over the last few years, significant efforts have been made in order to develop 5AR inhibitors (5ARI) to treat Benign Prostatic Hyperplasia because of excessive production of DHT.

Target Based Designing of Anthracenone Derivatives as Tubulin Polymerization Inhibiting Agents: 3D QSAR and Docking Approach.

Novel anthracenone derivatives were designed through in silico studies including 3D QSAR, pharmacophore mapping, and molecular docking approaches. Tubulin protein was explored for the residues imperative for activity by analyzing the binding pattern of colchicine and selected compounds of anthracenone derivatives in the active domain. The docking methodology applied in the study was first validated by comparative evaluation of the predicted and experimental inhibitory activity.

Design, synthesis and ex-vivo release studies of colon-specific polyphosphazene-anticancer drug conjugates.

Colon-specific azo based polyphosphazene-anticancer drug conjugates (11-18) have been synthesized and evaluated by ex-vivo release studies. The prepared polyphosphazene drug conjugates (11-18) are stable in acidic (pH=1.2) buffer which showed that these polymer drug conjugates are protected from acidic environment which is the primary requirement of colon specific targeted drug delivery.

Linaclotide-a novel secretagogue in the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation.

Irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are highly prevalent gastrointestinal disorders. Traditional symptoms based therapies had somewhat limited success and efficacy in addressing the disorders. Recently, linaclotide emerged as novel peptide capable of improving abdominal symptoms in patients suffering from IBS-C and CIC.

Design, synthesis and ex vivo evaluation of colon-specific azo based prodrugs of anticancer agents.

Colon-specific azo based prodrugs of anticancer agents like methotrexate (6), gemcitabine (7) and analogue of oxaliplatin (RTB-4) (8) were synthesized and characterized by modern analytical techniques. The prepared prodrugs were stable in acidic (pH 1.2) and basic (pH 7.

Synthesis and characterization of 3β-substituted amides of 17a-aza-D-homo- 4-androsten-17-one as potent 5α-reductase inhibitors and antimicrobial agents.

We herein report the synthesis of 3β-substituted amides of 17a-aza-D-homo-4-androsten-17-one (11a-11r) from commercially available Diosgenin as the starting material. The structures of newly synthesized compounds were confirmed by IR, (1)H NMR, (13)C NMR and mass spectrometry. All the synthesized analogues were tested for their 5α- reductase inhibitory and antimicrobial activity, some of them exhibit moderate to potent activity comparable to the reference drugs.

Enzalutamide: a novel anti-androgen with prolonged survival rate in CRPC patients.

Prostate cancer is the most common malignancy among men found to be the second leading cause of male cancer-related mortality due to development of resistance against androgen deprivation therapy (ADT). With the advancement in understanding of prostate cancer, numbers of agents have been emerged to target Androgen-Receptor (AR) signaling for the treatment of castration resistant prostate cancer (CRPC). Food and Drug Administration (FDA) has recently approved enzalutamide (XTANDI) for the treatment of CRPC.

Aflibercept: a novel VEGF targeted agent to explore the future perspectives of anti-angiogenic therapy for the treatment of multiple tumors.

Angiogenesis is the process of formation of new blood vessels due to over expression of VEGF (vascular endothelial growth factor) which plays a critical role in the growth and development of all solid tumor types. With the advancement in understanding of tumor angiogenesis and VEGF, there have been a number of agents developed to target VEGF for the treatment of cancer. These targeted agents can affect downstream VEGF signal transduction by unique mechanisms at different cellular and extracellular levels.

Synthesis, characterization of (Z)-N-(1-(2-(2-amino-3-(dimethylamino) methyl)phenyl)-5-phenyl-1,3,4, oxadiazol-3(2H)-yl)ethanone analogs as potent antimicrobial and hydrogen peroxide scavenging agents.

A series of (Z)-N-(1-(2-(2-amino-3-((dimethylamino) methyl) phenyl)-5-phenyl-1,3,4,oxadiazol-3(2H)- yl)ethanone derivatives was prepared and studied for its antimicrobial and antioxidant activities. Among the synthesized derivatives, compounds (7c) (Z)-N-(1-(2-(2-amino-3-((dimethylamino)methyl)phenyl)-5-phenyl-1,3,4-oxadiazol-3(2H)- yl)ethylidene)-4-chloroaniline, (7g) (Z)-N-(1-(2-(2-amino-3-((dimethylamino)methyl)phenyl)-5-phenyl-1,3,4-oxadiazol- 3(2H)-yl)ethylidene)-4-nitroaniline and (7i) (Z)-N-(1-(2-(2-amino-3-((dimethylamino)methyl)phenyl)-5-phenyl-1,3,4- oxadiazol-3(2H)-yl)ethylidene)-4-methoxyaniline were found to be the most effective antimicrobial compounds. While the compounds 7c and 7g were the most potent antioxidant compounds with significant hydrogen peroxide scavenging activity.

Cabazitaxel: a novel drug for hormone-refractory prostate cancer.

Cabazitaxel has recently been approved by FDA for the treatment of docetaxel resistant hormone-refractory prostate cancer. It has been developed by Sanofi-Aventis under the trade name of Jevtana. It is given in combination with prednisone/prednisolone and has passed the clinical trial over well-known drug mitoxantrone.

Synthesis and characterization of (E)-N'-(substituted benzylidene)isonicotinohydrazide derivatives as potent antimicrobial and hydrogen peroxide scavenging agents.

A series of (E)-N'-(substituted benzylidene)isonicotinohydrazide derivatives were synthesized by coupling isoniazid with differently substituted aldehydes and benzophenones in the presence of absolute ethanol along with catalytic amount of glacial acetic acid. The structure of all the synthesized compounds were confirmed and characterized by using various spectral technique like IR, 1H NMR, 13C NMR and mass spectroscopy. All the synthesized compounds were evaluated for their antimicrobial activity in terms of zone of inhibition, minimum inhibitory concentration, minimum bactericidal concentration and minimum fungicidal concentration in camparison to the standard drugs.

Synthesis and characterization of (Z)-N-(1-[2-{3-[(dimethylamino)methyl)]-2-methoxyphenyl}-5-(pyridin-4-yl)-1,3,4-oxadiazol-3(2H)-yl]ethylidene) benzenamine derivatives as potent antifungal agents.

In the present study, a series of (Z)-N-(1-[2-{3-[(dimethylamino)methyl)]-2-methoxyphenyl}-5-(pyridin-4-yl)-1,3,4-oxadiazol-3(2H)-yl]ethylidene)benzenamine derivatives have been synthesized and characterized by IR, 1H NMR and 13C NMR spectra. All the synthesized compounds were evaluated for their antifungal activity and were compared with the standard drug, clotrimazole. The compounds demonstrated excellent to weak antifungal activity.

Synthesis, characterization and evaluation of benzylidene analogues as a new class of potential antioxidant agents.

Seventeen analogues of benzylidene were synthesized and evaluated for in vitro hydrogen peroxide scavenging activity. The structure of the newly synthesized compounds were confirmed by elemental and spectral (IR, 1H-NMR, 13C-NMR) studies. The antioxidant activity of the titled compounds was evaluated.

Synthesis, characterization and evaluation of mannich bases as potent antifungal and hydrogen peroxide scavenging agents.

In the present study, (E)-2-{ [-2-(2,4-Dinitrophenyl)hydrazono]methyl} phenol (3) was synthesized and used as key intermediate for the synthesis of new Mannich bases. All the synthesized compounds were evaluated for their antifungal activity against three fungal strains Candida albicans, Candida tropicalis and Aspergillus niger and antioxidant activity. The structure of these compounds was confirmed by IR, 1H NMR and 13C NMR studies.

Synthesis and screening of substituted thiosemicarbazone derivatives: an approach towards novel anticonvulsant search.

A series of thiosemicarbazones of halogen substituted benzaldehydes, benzophenone and acetophenone were synthesized using an appropriate synthetic route and characterized by thin layer chromatography and spectral analysis. The anticonvulsant activity of synthesized compounds was established in three seizures models which includes maximal electroshock (MES), subcutaneous pentylene tetrazole (scPTZ) induced seizures and minimal neurotoxicity test. Five compounds out of 21 exhibited protection in MES test while only one compound showed protection in scPTZ screen.