A Validated Method for the Quantitation of Ciprofloxacin Hydrochloride Using Diffuse Reflectance Infrared Fourier Transform Spectroscopy

A quantitative method using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) was developed and validated for the estimation of ciprofloxacin in its tablet dosage forms. The solid-state samples were prepared by dilution in dry potassium bromide and were analyzed by FTIR spectrophotometer with DRIFT sampling technique. A linear relationship for the carbonyl peak area centered around 1709 cm−1 was observed in the range of 0.3–1.5% w/w with good correlation coefficient of 0.998. The percent recovery of ciprofloxacin in three marketed tablet dosage forms was in the range of 98.76 ± 0.27. The present reported method is precise, reproducible, and eco-friendly. DRIFTS may have a potential as an alternative method for qualitative and quantitative analysis of ciprofloxacin in bulk drugs and tablet dosage forms.</jats:p

Insight into the Structural Requirements of Urokinase-Type Plasminogen Activator Inhibitors Based on 3D QSAR CoMFA/CoMSIA Models

Urokinase-type plasminogen activator (uPA), a trypsin-like serine protease, has been implicated in large number of malignancies, tumor cell invasion, angiogenesis and metastasis; hence, the potent and selective inhibitors of uPA may therefore be therapeutically useful drugs for treatment of various forms of cancer. A three-dimensional quantitative structure−activity relationship (3D QSAR) study was performed on five different chemical series reported as selective uPA inhibitors employing comparative molecular field analysis (CoMFA)/comparative molecular similarity indices analysis (CoMSIA) techniques to investigate the structural requirements for substrates and derive a predictive model that may be used for the design of novel uPA inhibitors. ClogP has been used as an additional descriptor in the CoMFA analysis to study the effects of lipophilic parameters on activity. Inclusion of ClogP did not improve the models significantly and exhibited comparable correlation coefficients with CoMFA steric and electrostatic models. 3D QSAR models were derived for 2-pyridinylguanidines (training set N = 25, test set N = 8), 4-aminoarylguanidines and 4-aminoarylbenzamidines (training set N = 29, test set N = 8), thiophene-2-carboxamindines (training set N = 64, test set N = 19), 2-naphthamidines (training set N = 32, test set N = 8), and 1-isoquinolinylguanidines (training set N = 29, test set N = 7). The CoMFA models with steric and electrostatic fields exhibited r2cv 0.452−0.722, r2ncv 0.812−0.986, r2pred 0.597−0.870, whereas CoMFA ClogP models showed r2cv 0.420−0.707, r2ncv 0.849−0.957, r2pred 0.600−0.870. The CoMSIA models displayed r2cv 0.663−0.729, r2ncv 0.909−0.998, r2pred 0.554−0.855. 3D contour maps generated from these models were analyzed individually, which provides the regions in space where interactive fields may influence the activity. The superimposition of contour maps on the active site of serine proteases additionally helps in understanding the structural requirements of these inhibitors. Further, the predictive ability of 3D QSAR models was affirmed by predicting the activity of novel 2-naphthamidines. 3D QSAR models developed may be used in designing and predicting the uPA inhibitory activity of novel molecules

3D-QSAR Studies on 4,5-Dihydro-1H-pyrazolo [4,3-h] Quinazolines as Plk-1, CDK2/A and Aur-A Serine/Threonine Kinase Inhibitors

Background: The family of serine/threonine protein kinases is associated with peculiar tumor cell-cycle checkpoints which are overexpressed in proliferating tissues as well as in cancers, making them as potential targets for cancer chemotherapy. In the present paper, 3D-QSAR studies were carried out on 4,5-dihydro-1H-pyrazolo[4,3-h]quinazolines against serine/threonine protein kinases viz. polo-like 1 (Plk-1), cyclin dependent 2/A (CDK2/A) and Aurora-A (Aur-A) and their in vitro anti-proliferative activity on A2780 ovarian cancer cell line. Methods: 3D-QSAR models were derived using stepwise forward-backward partial least square (SWFB_PLS) regression method using VlifeMDS QSAR plus software and the docking calculations were carried out using Docking Server. Results: The derived statistically significant and predictive 3D-QSAR models exhibited correlation coefficient r2 in the range of 0.875 to 0.966 and predictive r2 in the range of 0.492 to 0.618. The hydrogen bond donor NH group joining the phenyl ring with quinazoline and terminal amide group were found to favored for Plk-1, CDK2/A and anti-proliferative activity. Estimated energy of binding of compound 45 with enzymes was in the range of -8.52 to -9.03. Conclusion: The results of 3D-QSAR studies may be useful in the development of new pyrazolo[ 4,3-h]quinazoline derivatives with better inhibitory activities against serine/threonine kinases. </jats:sec

3D-QSAR CoMFA studies on trypsin-like serine protease inhibitors: a comparative selectivity analysis

Abstract-A series of indole/benzoimidazole-5-carboxamidines have been reported to inhibit various trypsin-like serine proteases viz. uPA, tPA, factor Xa, thrombin, plasmin, and trypsin, which are involved in various types of pathophysiological conditions such as cancer progression, thrombosis etc. Inhibition of these protease enzymes may serve as therapeutic agents in various types of cancer as well serve as anticoagulant or antithrombotic agents. The dual inhibitory action may result in poor clinical candidates. 3D-QSAR models were generated for indole/benzoimidazole-5-carboxamidines using the CoMFA technique to study their selectivity trends toward various trypsin-like serine proteases. Molecular superimposition was carried out on the template structure using atom-based RMS fit method. The CoMFA models were established from the training set of 25-29 molecules and validated by predicting the activities of seven-eight test set molecules. The CoMFA models generated using steric and electrostatic fields for tPA, fXa, thrombin, plasmin, and trypsin inhibition exhibited better statistical significance than the CoMFA models generated using ClogP as an additional descriptor. Thus, the validated CoMFA models with steric and electrostatic fields were used to generate 3D contour maps, which may provide possible modification of molecules for better selectivity/activity. The present 3D-QSAR studies emphasize the selectivity trends of indole/benzoimidazole-5-carboxamidines, which may be obliging in designing novel selective serine protease inhibitors of therapeutic interest

Biological activities of imidazo[2,1-b][1,3,4]thiadiazole derivatives: A review

AbstractImidazo[2,1-b][1,3,4]thiadiazole heterocycle was discovered during the 1950s. Since then, many newer derivatives are being developed and evaluated for their biological profiles. The derivatives of imidazo[2,1-b][1,3,4]thiadiazoles are widely explored for their biological potential viz. antimicrobial, antifungal, anticancer, anticonvulsant, analgesic, antiinflammatory, anesthetic, and diuretic. They are also reported as potential enzyme inhibitors of cyclooxygenase, Jun kinase, carbonic anhydrase demonstrating their possible significance in target oriented drug design and discovery. The present review highlights the last six decades of research on biological activities of the imidazo[2,1-b][1,3,4]thiadiazoles

Estimation of MBC: MIC Ratio of Herbal Extracts against Common Endodontic Pathogens

Herbal extracts have evoked interest owing to the small number of terpenoids and phenolic compounds, which impart antimicrobial, antioxidant, and anti-inflammatory properties. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentration (MFC) of four herbal extracts (lemon grass oil, basil oil, peppermint oil, and Obicure tea extract) against endodontic pathogens along with the MIC: MBC/MFC ratio were evaluated. The antimicrobial activity by detecting the MIC of three essential oils and tea extract was evaluated against eight common endodontic pathogens by the broth dilution method, while MBC was detected by subculturing onto blood agar from the first –three to five tubes from the MIC dilution tubes (showing no turbidity), which were plated on blood agar. All herbal extracts proved to be effective antimicrobials against tested endodontic pathogens. Basil oil had a bacteriostatic effect on all the organisms (P 0.05). Tea extract had a bacteriostatic effect (P > 0.05) against all tested microbes except Actinomyces, Lactobacilli, Staphylococcus (S.) aureus, and Fusobacterium (F.) nucleatum. Lemon grass oil had a bactericidal effect against all the organisms and a bacteriostatic effect against Peptostreptococcus (P > 0.05). It can be concluded that basil oil showed a strong bactericidal effect on the test organisms. The MIC for the organisms ranged from 0.2 to 50 μg/ml