Chamarthi Naga Raju

Design, Synthesis and Anti Colon Cancer Activity Evaluation of Phosphorylated Derivatives of Lamivudine (3TC)

The novel phosphorylated derivatives of Lamivudine (5a-5l) as potential anti colon cancer agents are synthe- sized. These title compounds are designed based on the basic pyrimidine derivative lamivudine as a starting compound and reacted with various phosphorodichloridates followed by the introduction of bioactive groups at the phosphorus. Their structures were characterized by IR, 1 H, 13 C, 31 P NMR and mass spectral analyses. All the compounds were evaluated for their anti colon cancer activity against COLO-205 cell lines in vitro studies. Among them 5a and 5b emerged as lead compounds with 0.003 μM and 0.0001 μM values.

Identification of substituted (3, 2-a) pyrimidines as selective antiviral agents: Molecular modeling study

A series of novel substituted dihydropyrimidine and 5H-thiazolo [3, 2-a] pyrimidine derivatives were designed and synthesized as a potential target to discover drugs fighting against the viral diseases. The main objective of the present work is to carry out the QSAR studies for all the series of the compounds starting from 4a to 6j to find out their molecular descriptors and predict the biological properties. All of them are showing the best QSAR descriptors, hence chosen for the prediction of anti-viral activity against Newcastle disease virus (NDV). Initially their inhibitory activity was predicted by molecular docking of these compounds against haemaglutinin-neuraminidase (HN) protein using molecular operating environment (MOE) software. Based on the best affinity and highest docking scores 4b, 5b and 6b were assayed in vivo on NDV infected chicks and it was found that there is significant improvement in the survival of the chicks with the treatment (P<0.05). 4b and 6b showed better curative effect than 5b at the dose concentration of 40 mg/kg body weight of chicks. The results from molecular docking study and biological assays can be inferred to consider these molecules as potential antiviral drugs.

EcoFriendly Synthesis of Tetrahydropyrimidine Derivatives in Aqueous Medium Under Ultrasonic Irradiation

Abstract A simple, efficient, and ecofriendly procedure was developed for the synthesis of 2-substituted 1,4,5,6-tetrahydropyrimidine derivatives catalyzed by N-bromosuccinimide using ultrasonic irradiation in aqueous medium. Prominent advantages of this new method are good yields, aqueous medium, short reaction times, and easy workup procedure. The compounds were characterized by infrared, NMR, liquid chromatography–mass spectrometry, and elemental analyses. GRAPHICAL ABSTRACT

Ultrasound-Assisted Synthesis of Novel α-Aminophosphonates and Their Biological Activity

The synthesis of a series of novel α‐aminosubstituted phosphonates was accomplished by the reaction of various substituted aldehydes with an amine amlodipine (3‐ethyl 5‐methyl (±)2‐((2‐aminoethoxy)methyl)‐4‐(2‐chlorophenyl)‐6‐methyl‐1,4‐dihydropyridene‐3,5‐dicarboxylate) followed by diethylphosphite/dibutylphosphite in ethanol using SnCl2.2H2O as a Lewis acid catalyst, under conventional and ultrasonic irradiation. Their structures were established by analytical and spectral data. The title compounds showed good antibacterial, antifungal and antiviral activity depending on the nature of the bioactive groups at the α‐carbon.

Microwave-assisted neat synthesis of α-aminophosphonate/phosphinate derivatives of 2-(2-aminophenyl)benzothiazole as potent antimicrobial and antioxidant agents

GRAPHICAL ABSTRACT ABSTRACT A series of diethyl/ethylphenyl {2-(benzo[d]thiazol-2-yl)phenylamino}phosphonates and phosphinates were synthesized under microwave irradiation and neat conditions via Kabachnik-Fields reaction in high yields (80%–93%). The compounds were screened for antimicrobial and antioxidant properties. A few compounds showed effective antibacterial and antifungal activities at MIC value 12.5 μg/mL as compared with the standard at MIC value 6.25 μg/mL.

Synthesis and antioxidant activity of substituted-1,3,2-diazaphosphole 1-oxides.

Synthesis of 1‐substituted‐1,3,2‐diazaphosphole 1‐oxides (3a–l) were accomplished via a two‐step process. It involves the preparation of diazaphospholo 1‐oxide monochloride intermediate (2) and its subsequent reaction with phenols/amino acid esters in dry THF in the presence of triethylamine at 40–45°C. The structures of newly synthesized compounds were characterized by spectral and elemental analysis. The title compounds were evaluated for their in‐vitro antioxidant properties.

Synthesis, spectral, and antimicrobial evaluation of some new 8-membered phosphorus heterocyclic compounds

Synthesis of 9-substituted-8, 9 10, 11-tetrahydro-7H-7, 11-diaza-9λ5-phosphacycloocta [d,e] naphthalene-9-sulfides/selenides (4–13) was accomplished in three steps. 1,8-diamino naphthalene (2) was reacted with tris (bromomethyl) phosphine (1) in the presence of triethylamine in dry tetrahydrofuran (THF) under N2 atmosphere to form the corresponding intermediate (3). It was converted to the corresponding sulfide (4) and selenide (5) by the reaction with sulfur and selenium, respectively. The intermediates 4 and 5 were reacted with two achiral alcohols and two achiral amines to obtain the title compounds (6–13). The structures of the title compounds were established by elemental analysis and spectral data (IR, 1H, 13C, 31P NMR, and FAB mass). The antimicrobial activity of these compounds was evaluated and they exhibited significant activity.Graphical abstractSynthesis, spectral and antimicrobial evaluation of some new 8-membered phosphorus heterocyclic compoundsSynthesis of 9-substituted-8, 9 10, 11-tetrahydro-7H-7, 11-diaza-9λ5-phosphacycloocta [d,e] naphthalene-9-sulfides/selenides (4–13) was accomplished in three steps. 1,8-diamino naphthalene (2) was reacted with tris (bromomethyl) phosphine (1) in the presence of triethylamine in dry tetrahydrofuran (THF) under N2 atmosphere to form the corresponding intermediate (3). It was converted to the corresponding sulfide (4) and selenide (5) by the reaction with sulfur and selenium, respectively. The intermediates 4 and 5 were reacted with two achiral alcohols and two achiral amines to obtain the title compounds (6–13). The structures of the title compounds were established by elemental analysis and spectral data (IR, 1H, 13C, 31P NMR, and FAB mass). The antimicrobial activity of these compounds was evaluated and they exhibited significant activity. Synthesis, spectral and antimicrobial evaluation of some new 8-membered phosphorus heterocyclic compounds

New Urea and Thiourea Derivatives of Piperazine Doped with Febuxostat: Synthesis and Evaluation of Anti-TMV and Antimicrobial Activities

A series of new 4-(5-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-2-carbonyl)-N-(substituted phenyl)piperazine-1-carboxamides 8(a–e)/carbothioamides 8(f–j) were accomplished for biological interest by the simple addition of active functionalized arylisocyanates 7(a–e)/arylisothiocyanates 7(f–j) with 2-isobutoxy-5-(4-methyl-2-(piperazine-1-carbonyl)thiazol-5-yl)benzonitrile (4). Compound 4 was synthesized in high yields (94%) by the condensation reaction of febuxostat (1) with piperazine using a selective reagent such as propylphosphonic anhydride (T3P). Antiviral activity against Tobacco mosaic virus (TMV) and antimicrobial activity of the synthesized compounds were evaluated. Biological data revealed that 4-nitrophenyl substituted urea 8d, and 3-bromophenyl substituted thiourea 8f exhibited promising antiviral activities. Moreover, 4-fluorophenyl substituted urea 8a, 4-nitrophenyl substituted urea 8d, 3-bromophenyl substituted thiourea 8f, and 2,4-dichlorophenyl substituted thiourea 8j exhibited potent antimicrobial activity.

N-Phosphorylated Derivatives of 5-Nitroindazole as Antimicrobial and Antioxidant Agents and Docking Study Against DNA Gyrasea

GRAPHICAL ABSTRACT Abstract A series of new phosphoramidate derivatives 7a-l were synthesized by reacting 5-nitroindazole with 4-chlorophenyl dichlorophosphate (4), and then further with various bio-potent aromatic/hetero/alkyl amines 6a-l. All the newly synthesized compounds were characterized by spectroscopic data (IR, 1H, 13C, 31P NMR and mass) and elemental analysis. The products 7a-l were evaluated for their antioxidant activity (DPPH, H2O2 methods and IC50 values) and antimicrobial activity against the growth of Gram bacterial (positive and negative) and fungal pathogens. In the entire bio-screening data, we observed that 7j is the most active compound in terms of its antimicrobial and antioxidant activities. Further to know the binding interactions of title products with DNA GyraseA enzyme (E. coli), molecular docking studies were performed which revealed 7j and 7k exhibited high binding affinities towards the enzyme, DNA GyraseA (GyrA), and are higher than that of the standard antibiotic, streptomycin.

Synthesis, Spectroscopic Characterization, Antimicrobial and Antioxidant Activities of Novel Phosphorylated Derivatives of Amlodipine

Abstract A series of novel phosphorylated derivatives of Amlodipine were synthesized by the reaction of amlodipine with 2-chlorophenyl phosphorodichloridate in the presence of tetramethylguanidine in dry THF to form an intermediate product. The intermediate on further reaction with various aminoacid esters in the presence of tetramethylguanidine in dry THF afforded the title compounds. Their structures were characterized by IR, 1H, 13C, 31P NMR, mass, and elemental analyses. All the title compounds exhibited promising antimicrobial and antioxidant activities. Their bioactivity was greatly influenced by different groups present at the phosphorus. GRAPHICAL ABSTRACT